Adult ; China ; Diagnostic Errors ; Diphtheria ; diagnosis ; Female ; Humans

OBJECTIVETo compare the effects of doxycycline, losartan, and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats.

METHODSTwenty-four hours after the induction of AMI, the 254 survival rats were randomly assigned to the following groups and received drug treatment: (1) AMI controls (n=64), (2) doxycycline (30 mg x kg(-1) x d(-1), n = 63), (3) losartan (10 mg x kg(-1) x d(-1), n = 62), and (4) combination doxycycline and losartan (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65) treatment groups. Also, sham operated rats (n = 30) were selected randomly. Each group was further divided into three subgroups of 1, 2, and 4 weeks of treatment. After the completion of treatment, hemodynamic studies were performed. Then, the heart of rat was fixed and analyzed pathologically.

RESULTSExclusive of the dead rats and the hearts with the myocardial infarction size < 35% or > 50%, complete experimental data were obtained in 157 rats. Besides sham operated rats, there was no significant difference in myocardial infarction sizes among the 12 subgroups of AMI control and drug treatment groups (P> 0.05). Compared with sham operated rats, left ventricular end diastolic pressure (LVEDP) and left ventricular absolute weight and relative weight (LVAW and LVRW) were significantly increased in 1, 2, and 4 week subgroups of AMI controls (P < 0.05, P < 0.01, and P < 0.001, respectively), with LVEDP elevated more significantly in 4 week than in 1 and 2 week subgroups (P < 0.01); whereas the maximum rising and dropping rate of left ventricular pressure (+/-dp/dt) and its corrected value by left ventricular systolic pressure (+/-dp/dt/LVSP) were all significantly decreased only at 4 week subgroup of AMI controls (P < 0.001). Compared with AMI controls group, LVEDP was significantly decreased in all 1, 2, and 4 week subgroups of the three treatment groups (P < 0.05, P < 0.01, and P < 0.001, respectively); LVAW and LVRW were significantly decreased in 2 and 4 week subgroups of losartan and combination groups (P < 0.05, P < 0.01, P < 0.001, respectively), and in only 4 week subgroup in doxycycline (P < 0.05, P < 0.01, and P < 0.001, respectively); whereas the maximum dropping rate of left ventricular pressure and the corrected value of left ventricular pressure rising and dropping rate were significantly increased only in 4 week subgroups of all three treatment groups (P < 0.05, P < 0.01, respectively). There is no significant difference in all indices above among the three treatment groups at all three time points (P > 0.05).

CONCLUSIONIt is indicated that doxycycline can prevent left ventricular remodeling and improve its systolic and diastolic function after AMI in rats, with the equivalent effect to that of losartan. There seems no additive effect when the two drugs are used in combination.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Doxycycline ; therapeutic use ; Female ; Losartan ; therapeutic use ; Myocardial Infarction ; drug therapy ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; drug effects

OBJECTIVETo investigate the inhibitory activities of caffeoyl glucopyranoses purified from Balanophora japonica Makino on HIV entry and their mechanism.

METHODSHIV-1 Env pseudovirus was used to evaluate the anti-HIV-1 activity of those compounds. ELISA and molecular docking were used to study the mechanism of the actions of the active compounds.

RESULTSWe used the HIV-1 Env pseudovirus to test the anti-HIV-1 activity of the six phenolic compounds (final concentration 25 microg/ml), and found that only 1,2,6-Tri-O-caffeoyl-beta-D-glucopyranose (TCGP) and 1,3-Di-O-caffeoyl-4-O-galloyl-beta-D- glucopyranose (DCGGP) could effectively inhibit the entry of HIV-1 Env pseudovirus into the target cells in a dose-dependent manner, with IC(50) values of 5.5-/+0.2 and 5.3-/+0.1 microg/ml, respectively. These two compounds could also blocked the gp41 six-helix bundle formation. Molecular docking analysis suggested that they might bind to the hydrophobic cavity of the gp41 N-trimeric coiled-coil.

CONCLUSIONTCGP and DCGGP are potent HIV-1 entry inhibitors targeting gp41 and can serve as lead compounds for developing novel anti-HIV-1 microbicides for prevention of sexual HIV-1 transmission.

Anti-HIV Agents ; pharmacology ; Balanophoraceae ; chemistry ; Cell Line ; Gallic Acid ; analogs & derivatives ; pharmacology ; Glucose ; analogs & derivatives ; pharmacology ; HIV-1 ; drug effects ; Humans ; Hydrolyzable Tannins ; pharmacology ; Plant Extracts ; pharmacology

OBJECTIVETo study the relationship between inflammation and neointimal proliferation after coronary stent implantation in porcine model.

METHODSTwenty normal minipigs were randomly divided into group A (implanted with 316L bare metal stents), group B (implanted with 605L bare metal stents), group C (implanted with PLGA coating 605L stents), and group D (implanted with rapamycin-loaded PLGA coating 605L stents). Each minipig was implanted with two same stents in left anterior descending artery and right coronary artery. Four weeks later, the animals were sacrificed and histomorphometric measurements on the stent-segment coronary arteries were made to calculate the correlation between inflammation area and neointimal area.

RESULTSGroup D had the smallest neointimal area [(0.64 +/- 0.38) mm2, P < 0. 001] and inflammation area (median 0.00 mm2, P = 0.009) among all the groups, while there were no statistical differences among group A, B, and C in neointimal area [(2.09 +/- 0.90), (2.11 +/- 1.07), and (1.42 +/- 0.35) mm2 respectively] and in inflammation area (0.22 , 0.21, and 0.09 mm2, respectively). Bivariate correlation analysis showed that the inflammation area was positively correlated with the neointimal area (P < 0.001, correlation coefficient = 0.719). When stent type, mean injury score, and EEL area were adjusted, partial correlations analysis showed that the inflammation area was still positively correlated with the neointimal area (P = 0.01, correlation coefficient = 0.498).

CONCLUSIONInflammation promotes the neointimal proliferation after coronary stent implantation. Sirolimus-eluting stent may reduce the inflammatory response.

Animals ; Coronary Vessels ; pathology ; Drug-Eluting Stents ; adverse effects ; Inflammation ; pathology ; Neointima ; pathology ; Stents ; adverse effects ; Swine ; Swine, Miniature ; Tunica Intima ; pathology

OBJECTIVETo compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats.

METHODSAMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis.

RESULTSCompared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05).

CONCLUSIONBoth Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.

Adrenergic beta-Antagonists ; pharmacology ; Animals ; Apoptosis ; drug effects ; Atenolol ; pharmacology ; Female ; Metoprolol ; pharmacology ; Myocardial Infarction ; pathology ; Myocytes, Cardiac ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; biosynthesis ; genetics

OBJECTIVETo study the relationship between the change of coagulation and the clinicopathologic characteristics in patients with gallbladder cancer.

METHODSThe 64 gallbladder cancer patients (GBC group) and 60 cholecystitis patients (control group) had been reviewed from January 2007 to June 2013. The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), and thrombin time (TT) had been measured and compared between patients of GBC group and control group. The relationship of coagulation function and prognosis were analyzed.

RESULTSCompared with control group, APTT in GBC group ((29.0 ± 4.2) s) was significantly shortened (t = -4.265, P = 0.000) and PT ((11.5 ± 1.4) s), TT ((15.3 ± 3.5) s), Fib ((4.1 ± 0.9) g/L) were significantly increased in GBC group (t = 2.521, 4.147 and 4.365, all P < 0.05). The level of Fib was higher in patients with medium or poor-differentiated tumor cells (F = 4.069, P = 0.022), lymph metastasis (t = 2.640, P = 0.010) and advanced staging (II-IV) (t = 3.003, P < 0.01) than those of well-differentiated, non-lymph metastasis and early staging (0-I). The ratio of gallbladder cancer with hyperfibrinogenemia (32/64) was significantly higher than control group (11/60, χ(2) = 13.709, P < 0.01). In GBC group, compared with normal Fib patients, hyperfibrinogenemia patients showed significantly difference in clinicopathologic characteristics (χ(2) = 5.851-10.573, P < 0.05). The average survival period of hyperfibrinogenemia patients and normal Fib patients were 8.63 months and 16.73 months. The 1-, 3-year survival rate of patients with hyperfibrinogenemia were significantly lower than those with normal Fib (64.7%, 14.9% vs. 74.9%, 21.1%, P < 0.05).

CONCLUSIONPreoperative plasma level of Fib might be a new promising biomarker in patients with gallbladder cancer for evaluating disease progression and prognosis.

Adult ; Aged ; Aged, 80 and over ; Blood Coagulation ; Case-Control Studies ; Female ; Fibrinogen ; metabolism ; Gallbladder Neoplasms ; physiopathology ; Humans ; Male ; Middle Aged ; Prognosis ; Prothrombin Time

OBJECTIVETo determine the value of elective neck dissection in patients with clinically stage I (cT1N0M0) squamous cell carcinoma of the tongue.

METHODSThis was a retrospective study of patients with surgical treatment between November 1984 and November 1999. A total of 130 patients were included in the study, all of whom received operation of the primary site, meanwhile, 99 of whom underwent elective neck dissection simultaneously including level I -III or level I -IV neck dissection in 20 patients and level I - V neck dissection in 79 patients. Results Among all these patients, the rate of occult metastasis to the neck were 12. 0%. Local failure rate in patients with only local treatment, level I II, II, III/IV neck dissection and level I - V neck dissection were 25. 8%, 15. 0% and 7. 6% respectively. There were significant difference in regional failure between patients with only local treatment and patients with elective neck dissection (P < 0.05). Also, no significant differences were noted in the survival rate between patients with only local treatment, elective neck dissection (level I -III or level I -IV) and level I -V neck dissection (P > 0.05).

CONCLUSIONSElective neck dissection significantly reduced regional control failure but was not able to reduce distant metastasis or increase the overall survival. A prospective randomized study is worthwhile to further evaluate the benefit of elective neck dissection in the treatment of clinically stage I squamous cell carcinoma of the tongue.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; surgery ; Elective Surgical Procedures ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck Dissection ; Neoplasm Staging ; Retrospective Studies ; Tongue Neoplasms ; pathology ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo compare the effects of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) or peripheral endothelial progenitor cells (EPC) in mini-swine model of myocardial ischemia-reperfusion.

METHODSThe Mini-swine acute myocardial infarction and reperfusion model was created with 90 min occlusion of the left anterior descending coronary artery followed by reperfusion and the animals were then divided into BM-MNC group (3.54 x 10(8) +/- 0.90 x 10(8), n = 9), EPC group (1.16 x 10(7) +/- 1.07 x 10(7), n = 7) and control group (saline, n = 7). Echocardiography, hemodynamic measurements and myocardium infarction size were evaluated before and 4 weeks after intracoronary cell transplantations.

RESULTSThe net decrease from baseline to 4 weeks after transplantation of left ventricular ejection fraction (LVEF), left ventricular end systolic pressure, cardiac output and +dp/dt(max) were significantly attenuated post BM-MNC and EPC therapy compared to control group (all P < 0.05) and were similar between BM-MNC and EPC groups. Transplantation of BM-MNC and EPC also significantly decreased myocardial infarction size compared to control group.

CONCLUSIONAutologous intracoronary transplantation of BM-MNC or EPC in this model equally improved cardiac systolic function and reduced infarction area.

Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; Coronary Circulation ; Disease Models, Animal ; Endothelial Cells ; cytology ; Female ; Male ; Myocardial Reperfusion Injury ; therapy ; Stem Cells ; cytology ; Swine ; Swine, Miniature ; Transplantation, Autologous

OBJECTIVETo investigate the differentiation status of autologous bone marrow mononuclear cells (BM-MNC) and peripheral endothelial progenitor cells (EPC) transplanted into myocardial ischemia reperfusion injury region in swine.

METHODSBM-MNC marked with PKH26 (n = 9), EPC marked with CM-DiI (n = 7), phosphate buffer saline (control, n = 7) were transplanted into myocardial ischemia reperfusion injury region of swine by intracoronary artery injection. Specimens were harvested 4 weeks after injection for histological analysis (HE, immunochemical stain for vWF, alpha-sarcomeric-actin and fibronectin antibody). Cell differentiation was observed under transmission electronmicroscope.

RESULTSThe number of small blood vessels was similar between BM-MNC group and EPC group (13.39 +/- 6.96/HP vs.12.39 +/- 4.72/HP, P < 0.05), but was significantly higher than that of control group (P < 0.05). Responsive intensity of immunochemical stain for fibronectin antibody was significantly lower in BM-MNC and EPC groups than that in control group. Responsive intensity of immunochemical stain for alpha-sarcomeric-actin antibody was similar among the three groups. Cluster cells were observed in one swine from BM-MNC group which might relate to the proliferation of stem cells in situ. Immature endothelial cells and myocytes were also detected by transmission electronmicroscope in BM-MNC and EPC group.

CONCLUSIONBM-MNC and EPC transplanted into myocardial ischemia reperfusion injury region in swine stimulated the formation of blood vessels and inhibited fibrogenesis.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Endothelial Cells ; cytology ; transplantation ; Mesenchymal Stem Cell Transplantation ; Monocytes ; transplantation ; Myocardial Reperfusion Injury ; blood ; Stem Cells ; cytology ; Swine ; Swine, Miniature ; Transplantation, Autologous

BACKGROUNDAlthough thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study.

METHODSThis multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (age < or = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval > 3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow grade < or = 2. Bare-metal stent implantation was planned for all patients.

RESULTSAfter randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).

CONCLUSIONSThrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Thrombolytic Therapy