Objective To establish a model of pancreatic cancer induced by 7,12-dimethylbenzathracene (DMBA) in SD rats, and to detect the expression levels of RAD51 and Myc-associated factor X (MAX) and their effect on carcinogenesis of rat pancreas. Methods Ninety SD rats were randomly divided into 3 groups: a model group, an intervention group, and a control group. DMBA was directly implanted into the parenchyma of rat pancreas (the model group and the intervention group). Rats in the intervention group were treated with 1 mL trichostatin A (TSA) saline solution (1 μg/mL) via ip weekly. Rats within 3～5 months in the model group and the intervention group were executed and observed by macrograph and under microscope. Meanwhile, the rats in the control group were executed at 5th month. The EnVision~(TM) immunohistochemistry to assay the expression levels of RAD51 and MAX was used in conventional paraffin-embedded sections from the above pancreatic specimens.Results The incidence of pancreatic cancer in the model group within 3-5 months was 48.7% (18/37), including 17 ductal adenocarcinomas and 1 fibrosarcoma. The incidence of pancreatic cancer in the intervention group within 3-5 months was 33.3%(12/36), including 11 ductal adenocarcinomas and 1 fibrosarcoma. The maximal diameter of mass in the model group was significantly higher than that in the intervention group (P＜0.05). No pathological changes were found in pancreas of the control group and other extra-pancreatic main organs of the model group and the intervention group (such as the liver, biliary tract, gastrointestine tract, kidney, and lung). The positive rate of RAD51 was significantly higher in ductal adenocarcinoma in the model group, the intervention group, and the model group +the intervention group than those in corresponding groups of non-cancerous pancreatic tissues (P＜0.01), but the positive rate of MAX expression was opposite to RAD51 expression(P＜0.01). The positive tissues of RAD51 expression and/or negative tissues of MAX expression in non-cancerous tissues showed atypical-hyperplasia of ductal epitheli. Pacncreas of the control group showed the negative expression of RAD51 and positive expression of MAX. Two cases of fibrosarcoma showed the negative expression of RAD51 and MAX.Conclusion DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. The TSA might have an inhibitive effect on carcinogenesis and growth of rat pancreas. The over-expression of RAD51 and/or lose-expression might have important effect on carcinogenesis induced DMBA in rat pancreas.

Objective To explore the correlation between heart rate recovery after exercise test and disease severity in patients with chronic obstructive pulmonary disease(COPD)and assess its impact on the exercise capacity of COPD patients.Methods Arterial blood gas analysis, pulmonary lung function test and cardiopulmonary exercise testing were performed in 60 patients with stable COPD and 50 healthy volunteers.Based on the heart rate recovery after exercise test, COPD patients were divided into normal heart rate recovery group(n =41)and abnormal heart rate recovery group(n =19).Results The COPD patients had lower exercise capacity(peak oxygen uptake as percentage of predicted value, peak VO2％ pred)(66 ± 15vs.89±11, P＜0.01), peak heart rate [(134±21)vs.(149±13)beats/min, P＜0.01], heart rate recovery[(18 ± 9)vs.(27 ± 10)beats/min, P ＜ 0.01] and higher resting heart rate [(83 ± 13)vs.(77 ± 13)beats/min, P ＜0.01] than the controls.Compared with normal heart rate recovery group, forced expiratory volume in one second as percentage of predicted(FEV1 ％ pred)and exercise capacity decreased more significantly in abnormal heart rate recovery group(38 ± 15 vs.52 ± 16, P＜0.05 and 57 ± 12 vs.71 ±14, P ＜0.01).Heart rate recovery was significantly correlated with FEV1％ pred and peak V O2％ pred(r=0.42, P ＜ 0.01 and r =0.52, P ＜ 0.01).Multivariate regression analysis showed that heart rate recovery and FEV1 ％ pred could be used as independent predictors of exercise capacity in COPD patients.Conclusion In COPD patients, heart rate recovery is correlated with the degree of disease severity and it may be an independent predictor of exercise capacity.

OBJECTIVETo observe oxygen uptake efficiency plateau (OUEP, i.e.highest V˙O2/V˙E) and carbon dioxide output efficiency (lowest V˙E/V˙CO2) parameter changes during exercise in normal subjects.

METHODSFive healthy volunteers performed the symptom limited maximal cardiopulmonary exercise test (CPET) at Harbor-UCLA Medical Center. V˙O2/V˙E and V˙E/V˙CO2 were determined by both arterial and central venous catheters. After blood gas analysis of arterial and venous sampling at the last 30 seconds of every exercise stage and every minute of incremental loading, the continuous parameter changes of hemodynamics, pulmonary ventilation were monitored and oxygen uptake ventilatory efficiency (V˙O2/V˙E and V˙E/V˙CO2) was calculated.

RESULTSDuring CPET, as the loading gradually increased, cardiac output, heart rate, mixed venous oxygen saturation, arteriovenous oxygen difference, minute ventilation, minute alveolar ventilation, tidal volume, alveolar ventilation and pulmonary ventilation perfusion ratio increased near-linearly (P < 0.05-0.01, vs.resting); arterial oxygen concentration maintained at a high level without significant change (P > 0.05); stroke volume, respiratory rate, arterial partial pressure of carbon dioxide, arterial blood hydrogen ion concentration and dead space ventilation ratio significantly changed none-linearly (compare resting state P < 0.05-0.01).OUE during exercise increased from 30.9 ± 3.3 at resting state to the highest plateau 46.0 ± 4.7 (P < 0.05 vs.resting state), then, declined gradually after anaerobic threshold (P < 0.05-0.01, vs.OUEP) and reached 36.6 ± 4.4 at peak exercise. The V˙E/V˙CO2 during exercise decreased from the resting state (39.2 ± 6.5) to the minimum value (24.2 ± 2.4) after AT for a few minutes (P > 0.05 vs.earlier stage), then gradually increased after the ventilatory compensation point (P < 0.05 vs.earlier stage) and reached to 25.9 ± 2.7 at peak exercise.

CONCLUSIONSCardiac and lung function as well as metabolism change during CPET is synchronous.In the absence of pulmonary limit, appearing before and after anaerobic threshold, OUEP and lowest V˙E/V˙CO2 could be used as reliable parameters representing the circulatory function.

Arteries ; Blood Gas Analysis ; Blood Pressure ; Carbon Dioxide ; metabolism ; Cardiac Output ; Exercise ; physiology ; Exercise Test ; Heart ; Heart Rate ; Hemodynamics ; Humans ; Lung ; Oxygen ; metabolism ; Oxygen Consumption

Objective: To investigate the expression of syndecan-1 and syndecan-2 and their clinicopathological significance in patients with gallbladder squamous cell (SC)/adenosquamous carcinoma (ASC) and adenocarcinoma (AC). Methods: A total of 126 patients with SC/ASC (n=46) and AC (n=80) were included in this study. The expression levels of syndecan-1 and syndecan-2 were detected by Envison™ immunohistochemistry assay. The clinical and prognostic significance of syndecan-1 and syndecan-2 were analyzed. Results: In the 46 SC/ASC samples, syndecan-1 and syndecan-2 were positively expressed in 29 (63.0%) and 28 (60.9%) tumor tissues, respectively. (Positive expression was defined based on the staining in the component of squamous cell carcinoma. That is to say, the tissue which adenocarcinoma part was positively stained, but squamous cell carcinoma part was negatively stained is also regarded as negative.) In the 80 AC samples, 47 (58.8%) cases showed syndecan-1 positive expression, and 51 (63.8%) showed syndecan-2 positive expression. There was no significant difference in the positive rates of syndecan-1 and syndecan-2 between SC/ASC and AC groups (P>0.05 for all). The levels of syndecan-1 and syndecan-2 were associated with tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in SC/ASC patients (P<0.05 for all). However, their expression was associated with tumor differentiation, tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in AC patients (P<0.05 for all). The Kaplan-Meier survival analysis of SC/ASC and AC patients revealed that the average survival time for patients with positive syndecan-1 and syndecan-2 expression was significantly shorter than that of those with negative expression (P<0.01 for all). Cox multivariate analysis indicated that syndecan-1 and syndecan-2 expression were independent unfavorable prognostic factors for SC/ASC and AC patients (P<0.05 for all). Conclusion The syndecan-1 and syndecan-2 expression are associated with the tumor progression and poor prognosis in patients with gallbladder SC/ASC and AC.

OBJECTIVETo assess the cardiopulmonary exercise testing (CPET) derived performance of oxygen uptake and ventilation efficiency parameters, including oxygen uptake efficiency plateau (OUEP) , oxygen uptake efficiency slope (OUES), V·E/V·CO2 slope and lowest V·E/V·CO2, in patients with end-stage chronic heart failure (CHF) and evaluate their clinical value on monitoring cardiac function and hemodynamic status.

METHODSA total of 26 end-stage CHF patients considered for heart transplantation were enrolled in this study. CPET, echocardiography and invasive hemodynamic examinations with Swan-Ganz flowing balloon catheter were performed. Correlation analysis was made between oxygen uptake and ventilation efficiency parameters from CPET and echocardiographic and hemodynamic parameters.

RESULTSOUEP and OUES showed good correlation with peak oxygen consumption (peak V·O2) (r = 0.535, P < 0.01;r = 0.840, P < 0.001). In end-stage CHF patients, the slope of OUEP with respect to peak V·O2 is about 32, but the slope of OUES with respect to peak V·O2 is only about 2. The difference was 16 times. The change of OUEP was more sensitive and significant than those of OUES and peak V·O2 (P < 0.05). OUEP, peak V·O2 (%pred), V·E/V·CO2 slope and lowest V·E/V·CO2 were all correlated well with non-invasive hemodynamic parameters peak cardiac output (r = 0.535, P < 0.01; r = 0.652, P < 0.001; r = -0.640, P < 0.001; r = -0.606, P = 0.001 respectively) and peak cardiac index (r = 0.556, P < 0.01;r = 0.772, P < 0.001; r = -0.641, P < 0.001; r = -0.620, P < 0.001 respectively) derived from CPET, but not correlated with invasive hemodynamic parameters cardiac output and cardiac index at rest (P > 0.05). Both peak V·O2 (%pred) and V·E/V·CO2 slope were significantly correlated with invasive hemodynamic parameters systolic pulmonary arterial pressure (r = -0.424, P < 0.05; r = 0.509, P < 0.01) and mean pulmonary arterial pressure (r = -0.479, P < 0.05; r = 0.405, P < 0.05). Peak V·O2 (%pred) was also significantly correlated with pulmonary capillary wedge pressure (r = -0.415, P < 0.05), and V·E/V·CO2 slope was significantly correlated with pulmonary vascular resistance (r = 0.429, P < 0.05).

CONCLUSIONSThe oxygen uptake and ventilation efficiency parameters derived from CPET, including peak V·O2, OUEP, lowest V·E/V·CO2 and V·E/V·CO2 slope etc, are objectively monitoring and evaluating cardiac function and hemodynamic status. And they are useful for optimizing clinical management of patients with end-stage CHF.

Cardiac Output ; Chronic Disease ; Exercise Test ; Heart Failure ; physiopathology ; Hemodynamics ; Humans ; Oxygen ; metabolism ; Oxygen Consumption ; Pulmonary Wedge Pressure