Objective To determine the correlation between mouse maerophage metalloelastase (MME)and vascular endothelial growth factor(VEGF)expression involved in angiogenesis of colon cancer.Methods A eDNA fragment coding for domainsⅠandⅡof MME was transfected into murine CT-26 colon cancer cells that were MME deficient.The enzymatic activity of recombinant MME was confirmed by cleavage of native substrate in vitro.An orthotopic implantation model was established by using MME-transfected cells and control cells.Tumor samples were subjected to in situ hybridization (ISH)and immunohistochemical staining(IHC)to detect expressions of MME and VEGF.The microvessel counting was used to assess angiogenesis of murine colon tumors.Results It was demon- strated that the tumor growth was significantly inhibited in MME-transfected group compared with pcDNA3.1 transfected and nontransfected groups(P＜0.001).It was also found that,compared with pcDNA3.1-transfected and nontransfected groups,the microvessel formation in MME transfected group was significantly reduced(P＜0.001).The expression of VEGF mRNA and protein was significantly lower in MME-transfected group than those in the controls,as demonstrated by ISH(MME-transfected group versus pcDNAa.1-transfected group,P=0.028;and versus nontransfected group,P=0.003) and by IHC(MME-transfected group versus pcDNA3.1-transfected group,P=0.025;and versus non- transfected group,P=0.008).Conclusions The MME gene transfected into murine colon cancer cells can effectively suppress the growth of orthotopic tumors by inhibition of vaseularity.Both MME and VEGF gene expression is highly associated with the vascularity of tumors,which may depend on a hal- ance between MME and VEGF expression.

OBJECTIVETo investigate the clinical significance of plasmic homocysteine (Hcy), folate (FA) and Vitamin B(12) (VitB(12)) in patients with ulcerative colitis (UC).

METHODSPlasmic Hcy in 112 cases of UC patients and 110 controls were detected by HPLC-FD method. Plasmic FA, VitB(12) in 76 cases of UC patients and 12 controls were detected by enzyme-linked immunosorbent assay (ELISA) method.

RESULTSThe level of plasmic Hcy in UC patients was(11.27±7.26) μmol/L, significantly higher than that in controls[(8.19±4.81) μmol/L, P<0.05], and was not significantly correlated with disease index, extent and duration of UC(P>0.05). The level of FA and VitB(12) in UC patients were (7.64±1.95) nmol/L and (108.64±32.22) pmol/L respectively, lower than those in controls[(9.14±1.23) nmol/L and (112.64±33.33) pmol/L, P<0.05]. The level of plasmic Hcy was negatively correlated with the level of FA and VitB(12) in UC patients(P<0.05). The level of plasmic FA decreased to some extent with UC disease duration.

CONCLUSIONPlasmic Hcy is elevated in UC patients, which may be related to the decrease of FA and VitB(12).

Adolescent ; Adult ; Aged ; Case-Control Studies ; Colitis, Ulcerative ; blood ; Female ; Folic Acid ; blood ; Homocysteine ; blood ; Humans ; Male ; Middle Aged ; Vitamin B 12 ; blood ; Young Adult

OBJECTIVETo evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.

METHODSAMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n = 6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI.

RESULTSMagnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/- 3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/- 1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05) compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs. 40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs. 41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR-MNC transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2) were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05), myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR-MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3 +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR-MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/- 0.2, P < 0.05).

CONCLUSIONSMagnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size, improved cardiac function. MR-MSC is superior to MR-MNC on improving cardiac function.

Animals ; Disease Models, Animal ; Magnetic Resonance Imaging ; Male ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; therapy ; Swine ; Swine, Miniature ; Treatment Outcome

OBJECTIVETo evaluate the effectiveness and safety of mosapride on treatment of functional dyspepsia.

METHODSRandomized controlled clinical trial was conducted and patients suffered from functional dyspepsia were included. 5 mg mosapride was given three times daily for 4 weeks in the treatment group. 10 mg domperidone was given three times daily for 4 weeks as control. Changes on symptom score, gastric empty or new occurring events were included as outcomes.

RESULTS231 patients suffered from functional dyspepsia were selected by inclusion and exclusion criteria from August 15 to Oct 22, 1999. Of these, 108 (46.8%) were males, versus 123 (53.2%) females and 118 (51.2%) in the treatment group and 113 (48.9%) as controls. 222 (96.1%) patients were followed up. Results showed that the total efficacy rates in early satiety and abdominal distension were 84.5% and 90.1% in mosapride after the 2 weeks of treatment. Mosapride seemed to be more effective in improving symptoms of belching and heartburn than that in controls (P < 0.05). In 4 weeks, the total efficacy in improving symptoms of abdominal distention and belching showed more effective in mosapride than that in controls (P < 0.05). Decrease of symptoms score was more in mosapride than that in controls (P < 0.05). Mosapride was less effective in controls in improving the gastric empty in terms of proportion (46.2% vs. 25.9%, P = 0.020) and range (46.2% vs. 24.0%, P = 0.003). Side effects would include diarrhea, constipation, headache, dizziness, insomnia, skin scare and the like. There was no significant difference between the two groups (9.6% in mosapride vs. 14.0% in controls).

CONCLUSIONMosapride was safe and effective in improving the symptoms and gastric empty of functional dyspepsia.

Adult ; Benzamides ; adverse effects ; therapeutic use ; Dyspepsia ; drug therapy ; Female ; Gastrointestinal Agents ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Morpholines ; adverse effects ; therapeutic use ; Treatment Outcome

BACKGROUNDBecause no data regarding the comparison of crush stenting with paclitaxel (PES) or sirolimus eluting stents (SES) for coronary bifurcate lesions have been reported, we compared the clinical outcomes of these two types of stents.

METHODSTwo hundred and thirty patients with 242 bifurcate lesions were enrolled in a prospective, nonrandomized trial. Primary endpoints included myocardial infarction, cardiac death and target vessel revascularization at 8 months.

RESULTSAll patients were followed up clinically and 82% angiographically at 8 months. Final kissing balloon inflation was performed in 72% in the PES and 75% in the SES groups (P>0.05). Compared to the SES group, PES group had a higher late loss and incidence of restenosis (P=0.04) in the prebifurcation vessel segment. The postbifurcation vessel segment in the PES group had a greater late loss ((0.7+/-0.6) mm vs (0.3+/-0.4) mm, P<0.001) and higher restenosis in the side branch (25.5% vs 15.6%, P=0.04) when compared to the SES group. There was significant difference of insegment restenosis in the entire main vessel between PES and SES groups (P=0.004). Target lesion revascularization was more frequently seen in the PES group as compared to the SES group (P=0.01). There was significant difference in the accumulative MACE between these two groups (P=0.01). The survival rate free from target lesion revascularization was significantly higher in the SES group when compared to the PES group (P<0.001).

CONCLUSIONSES is superior to PES in reducing restenosis and target lesion revascularization by 8-month follow-up after crush stenting for bifurcate lesions.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Prospective Studies ; Sirolimus ; administration & dosage

OBJECTIVETo evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.

METHODThis is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study.

RESULTS(1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.

CONCLUSIONThis study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; administration & dosage ; China ; Double-Blind Method ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Imidazoles ; adverse effects ; therapeutic use ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Olmesartan Medoxomil ; Tetrazoles ; adverse effects ; therapeutic use

BACKGROUNDSuperparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).

METHODSAn AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.

RESULTSMR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.

CONCLUSIONSWe demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.

Animals ; Cell Survival ; Contrast Media ; Ferric Compounds ; Magnetic Resonance Imaging ; methods ; Male ; Myocardial Infarction ; diagnosis ; pathology ; Stem Cells ; cytology ; Swine

BACKGROUNDHypertrophic obstructive cardiomyopathy (HOCM) carries an increased risk for sudden cardiac death. No data regarding the percutaneous transseptal myocardial ablation (PTSMA) and epicardial left ventricular pacing (LVP) were reported.

METHODSSeven patients with recurrent symptoms and increased resting left ventricular outflow tract pressure gradient (LVOTG) after PTSMA and another 14 patients with HOCM without history of PTSMA were studied. Both resting and dobutamine stress echocardiography, PTSMA and LVP were routinely performed.

RESULTSIn patients without previous PTSMA procedure, mild reduction of resting LVOTG was detected at 5 minutes after left ventricular pacing, and this reduction became significant at 10 minutes. All patients were divided into successful and unsuccessful groups according to their response to LVP. In contrary to patients in unsuccessful group, resting and R-S2 stimuli-induced LVOTG during PTSMA procedure were decreased dramatically ((9 +/- 5) mmHg vs (58 +/- 12) mmHg, (12 +/- 2) mmHg vs (113 +/- 27) mmHg, P < 0.001). Analysis of Logistic regression demonstrated that only LVOTG level during left ventricular pacing was an independent factor predicting the reduction of LVOTG immediately after PTSMA (odds ratio (OR), 0.59; 95% CI 2.67 to 5.82; P = 0.0002).

CONCLUSIONLeft ventricular endocardial temporary pacing plays a critical role in predicting acute effect on the reduction of LVOTG immediately after PTSMA procedure.

Adult ; Cardiac Pacing, Artificial ; Cardiomyopathy, Hypertrophic ; diagnostic imaging ; physiopathology ; therapy ; Catheter Ablation ; Echocardiography ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Pressure ; Ventricular Function, Left

BACKGROUNDMesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging.

METHODSAcute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01).

RESULTSA total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group.

CONCLUSIONTransplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.

Animals ; Blotting, Western ; Cell Survival ; Disease Models, Animal ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; physiopathology ; therapy ; Swine ; Ventricular Function, Left

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.