This research explored the synergistic effects and the potential mechanisms of RCE-4 and various nonsteroidal anti-inflammatory drugs (NSAIDs) on the proliferation of cervical cancer Ca Ski cells. The MTT assay and CalcuSyn V2.0 software were used to detect cell proliferation and calculate the combination index (CI); the expression levels of various proteins were analyzed using Western blot assay; mitochondrial membrane potential (MMP) was assessed using JC-1 staining; acridine orange/ethidium bromide (AO/EB) double-fluorescence staining was used to detect the apoptosis of Ca Ski cells; a co-immunoprecipitation (Co-IP) assay was used to analyze the relative content of Bcl-2-Beclin 1 complex in Ca Ski cells. The results demonstrate that the combination of RCE-4 and NSAIDs increases the inhibition of Ca Ski cells compared to the single-RCE-4 group, and celecoxib provided the best synergistic effect among the four NSAIDs tested, with a CI of 0.32. The combination of RCE-4 and celecoxib significantly down-regulated the expression of cyclooxygenase-2 (COX-2) and nuclear transcription factor-κB (NF-κB), and promoted the expression of non-steroidal anti-inflammatory drugs activity gene-1 (NAG-1). In addition, autophagy induced by RCE-4 was markedly inhibited in combination with celecoxib, which was associated with down-regulation of the expression of microtubule-associated protein 3 (LC3)-II, Beclin 1, p62 and autophagy-related gene (ATG) 3/4B/5/7/14. RCE-4-induced apoptosis was significantly enhanced by altering the depolarization of mitochondrial membrane potential and the expression of B cell lymphoma-2 (Bcl-2), B cell lymphoma-xl (Bcl-xl), Bcl-2 associated X protein (Bax), Bcl-2/Bcl-xl-associated death promoter (Bad) and cleaved cysteinyl aspartate specific proteinase (cleaved-caspase) 3/7/9. Furthermore, the formation of the Bcl-2-Beclin 1 complex was significantly inhibited in Ca Ski cells treated with RCE-4 in combination with celecoxib. Taken together, this research shows that the combination of RCE-4 and celecoxib has a significant synergistic effect on the proliferation of Ca Ski cells by promoting apoptosis, inhibiting autophagy and disturbing the formation of the Bcl-2-Beclin 1 complex, which may be a novel strategy to increase the sensitivity of anti-cervical cancer drugs.

Aneurysm ; complications ; therapy ; Cardiac Catheterization ; instrumentation ; Child ; Heart Septal Defects, Ventricular ; complications ; therapy ; Humans ; Septal Occluder Device

Acute Disease ; Bone Neoplasms ; diagnosis ; secondary ; Carcinoma, Squamous Cell ; classification ; diagnosis ; Humans ; Hypercalcemia ; complications ; Lung Neoplasms ; complications ; diagnosis ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology

AIMTo study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms.

METHODSIsolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed.

RESULTSGEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)).

CONCLUSIONGEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

Animals ; Cardiotonic Agents ; pharmacology ; Cyclic AMP ; metabolism ; Genistein ; pharmacology ; Guinea Pigs ; Heart Ventricles ; drug effects ; In Vitro Techniques ; Male ; Myocardial Contraction ; drug effects ; Protein-Tyrosine Kinases ; metabolism

OBJECTIVETo study the role of hypoxia-inducible factor 1 alpha (HIF1alpha) on knee cartilage degeneration,and to explore the effects and mechanisms of Chinese herbal compound Yiqi Huayu prescription on HIF-1alpha gene knockout mice on knee cartilage degeneration.

METHODSThe 4-month and 6-month HIF-1alpha gene knock out mice were obtained by interbreeding, and divided into HIF-1alpha +/+ 4-month mice group,HIF-1alpha -/- 4-month mice group,HIF-1alpha +/+ 6-month mice group and HIF-1alpha -/- 6-month mice group, 3 mice in each group. And then the 2-month-old HIF-1alpha gene knock out mice were randomly divided into Yiqi Huayu prescription group and physiological saline group. There were 6 mice in each group. After 2 months' drug administration, the knee joint of mice was collected, and the Mankin score were evaluated; Safranine-fast green staining, HE Staining, and immunohistochemistry analysis for VEGF, Col X, Col II, MMP-13 and Sox-9 were performed erespectively.

RESULTS(1) Compared to the results in the HIF-1alpha+/+ mice groups, the HIF-1alpha-/- mice developed aging related cartilage loss and bony tissue appearance, cartilage defects increased,and cells reduced. In HIF-1alpha-/-4-month mice and 6-month mice group, the expresion of Col II and Sox9 decreased, and the expression of Col X, MMP-13 and VEGF increased. (2) Compared to the physiological saline group, the ossification and defect of knee joint cartilage reduced of mice in the Yiqi Huayu prescription group, the cartilage cell distribution was more uniform, and the total number of cells increased. The expression of type II collagen and Sox9 protein increased, expression of Col X, MMP-13 and VEGF protein decreased of mice in the Yiqi Huayu prescription group.

CONCLUSIONThe knee cartilage degenerates in the HIF-1alpha cKO mice, and the degeneration increased with age adding. The Yiqi Huayu prescription can delay the degeneration of knee cartilage of HIF-1alpha cKO mice.

Animals ; Cartilage Diseases ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; deficiency ; genetics ; Joint Diseases ; drug therapy ; genetics ; metabolism ; Knee Joint ; metabolism ; physiopathology ; Male ; Mice ; Mice, Knockout

Objective To evaluate the feasibility and safety in the treatment of liver cancer located under the diaphragm with cool-tip radiofrequency ablation(RFA)percutaneously under CT guidance.Methods 20 patients with total 25 lesions were treated by CT-guided RFA with cool-tip electrode involving the induced necroses.The postoperative efficacy was evaluated by enhanced CT or MRI.Results 72% lesions were completely necrotized(18/25),28% lesions were majorly necrotized(7/25).No severe complications occurred. Conclusion CT-RFA with cool-tip electrode is effective and safe in treating liver cancer located under the diaphragm.

Objective To compare diagnostic value of ~(18)F-fluoredeoxyglucose (FDG) PET/CT with contrast-enhanced CT in detecting primary hepatic carcinoma and postoperative recurrence.Methods Twenty-five cases of primary hepatic carcinoma or postoperative recurrent tumor underwent whole-body ~(18)F-FDG PET/CT and contrast-enhanced CT within one week's interval.They were retrospectively reviewed and the difierences between these two modalities were investigated.Results Of these 25 cases,there were 13 cases with primary hepatocellular carcinoma.1 case with intrahepatic cholangiocarcinoma and 11 cases with postoperative recurrence.The sensitivity of 18 F-FDG PET/CT and contrast-enhanced CT in diagnosing primary hepatic carcinoma was 78.6%(11/14) and 92.9%(13/14),and sensitivity in diagnosing postoperative recurrent was 100.0%(11/11) and 63.6%(7/11) respectively.Conclusion Contrast-enhanced CT may have a slight advantage over PET/CT in detecting primary hepatic carcinoma,but ~(18)F-FDG PET/CT combined with contrast-enhanced CT has even greater accuracy.Meanwhile,~(18)F-FDG PET/CT has better diagnostic accuracy in detection of postoperative recurrent tumor.

OBJECTIVEto explore the feasibility of evaluating viable myocardium with two-dimensional strain imaging combined with adenosine stress echocardiography.

METHODSacute myocardial infarction and reperfusion model was made by ligating anterior descending coronary artery for 90 minutes followed by 120-minute reperfusion in 15 healthy mongrel dogs. Images were acquired at baseline and after reperfusion. Adenosine was then infused and image acquisition repeated. Regional peak-systolic strain in radial, circumferential and longitudinal motion on anterior wall and anterior septum were measured. TTC staining served as a "gold standard" to define viable and nonviable myocardium. The ratio of infarct area (S(N)) to total area (S) was calculated and viable myocardium was defined with S(N)/S ≤ 50%.

RESULTSat baseline, RS(peak sys), CS(peak sys) and LS(peak sys) were similar between viable (n = 37) and nonviable myocardial segments (n = 53) and significantly decreased after reperfusion in both viable and nonviable myocardial segments. Compared with values obtained after reperfusion, LS(peak sys) and RS(peak sys) remained unchanged in nonviable myocardial segments and significantly increased in viable myocardial segments after adenosine (P < 0.05). Post adenosine RS(peak sys) was negatively correlated with S(N)/S and CS(peak sys) and LS(peak sys) were positively correlated with S(N)/S. With ΔRS(peak-sys) (before and after adenosine) ≥ 13.5%, the sensitivity was 83.8% and specificity was 83.0% for distinguishing viable from nonviable myocardial segment. With ΔLS(peak sys) ≥ 11% as cutoff value, the sensitivity was 78.4% and specificity was 88.7% for distinguishing viable from nonviable myocardial segment. Combining ΔRS(peak sys) and ΔLS(peak sys), the sensitivity and specificity for distinguishing viable from nonviable myocardial segment were 91.9% and 79.2%, respectively.

CONCLUSIONStwo-dimensional strain imaging combined with adenosine stress echocardiography could quantitatively identify viable and nonviable myocardium.

Animals ; Disease Models, Animal ; Dogs ; Echocardiography, Stress ; methods ; Myocardial Infarction ; diagnostic imaging ; Myocardial Reperfusion Injury ; diagnostic imaging ; Myocardium ; pathology ; Tissue Survival

OBJECTIVESTo observe the clinical and coronary features of patients with systemic lupus erythematosus (SLE) and coronary artery disease (CAD).

METHODSAmong 2877 SLE inpatients (age ≥ 18 years, male 363, female 2514) admitted in the Peking Union Medical College Hospital between January 1999 to October 2009, 33 patients [mean age (50.7 ± 12.8) years] were diagnosed with CAD and coronary angiogram was available in 20 out of these 33 patients. Clinical and coronary features of these patients were retrospectively reviewed.

RESULTSThe incidence of CAD was significantly higher in male SLE patients than in female patients [2.48% (9/363) vs. 0.95% (24/2514), P = 0.022]. Patients with secondary antiphospholipid syndrome were more likely to suffer from CAD [5.76% (8/139) vs. 0.91% (25/2738), P < 0.001]. Myocardial infarction was the major form of CAD (24/33). Coronary artery angiographic changes included coronary stenosis and occlusions, coronary aneurysms and acute thrombosis and multi-vessel lesions was found in 75.0% (15/20) patients with SLE and CAD.

CONCLUSIONSMale SLE patients and patients with secondary antiphospholipid syndrome are at higher risk for CAD. Myocardial infarction and multi-vessel lesions are common in SLE patients with CAD.

Adolescent ; Adult ; Aged ; Antiphospholipid Syndrome ; complications ; Coronary Angiography ; Coronary Artery Disease ; complications ; pathology ; Female ; Humans ; Lupus Erythematosus, Systemic ; complications ; pathology ; Male ; Middle Aged ; Risk Factors ; Young Adult

OBJECTIVETo compare clinical characteristics among premenopausal women with coronary arterial disease (CAD) with or without atherosclerosis (AS) and postmenopausal women with CAD.

METHODSThe clinical and coronary angiographic data, traditional risk factors (age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history) were compared among premenopause (Pre-M, n=42) and post-menopause (Post-M, n=172) women with CAD as well as Pre-M patients with non-AS CAD (non-AS CAD, n=8).

RESULTSCompared with the Post-M patients with CAD, Pre-M CAD patients had significantly fewer traditional risk factors, such as hypertension, diabetes and hypercholesterolemia, significantly more acute coronary syndrome and fewer previous history of chest pain, significantly more single vessel lesion and lower Gessini score (all P < 0. 01). The logistic regression results showed that obesity is an independent risk factor for the development of CAD in premenopausal women (OR = 3. 655, 95% CI: 1. 5-11.59, P = 0.028). Hypertension (OR = 4.73, 95% CI: 0.991-22.589, P = 0.051) and hypercholesterolemia (OR = 4.68, 95% CI: 0.971-22.564, P = 0.055) might also contribute to the development of CAD in these patients. Clinical characteristics were similar between Pre-M and non-AS CAD patients (P > 0.05).

CONCLUSIONSPre-M CAD patients had less traditional risk factors and lower coronary lesion score compared to post-M CAD patients. Obesity is an independent risk factor for Pre-M CAD. Non-AS coronary artery disease is also an important reason for the development of coronary arterial events in premenopausal women.

Adult ; Aged ; Atherosclerosis ; complications ; Cohort Studies ; Coronary Artery Disease ; complications ; Female ; Humans ; Middle Aged ; Premenopause ; Risk Factors