The suppressive effects of Britannin (Bri) on human liver cancer through inducing apoptosis and autophagy via AMPK activation regulated by ROS.

Britannin (Bri), isolated from Inula aucheriana, is a sesquiterpene lactone (SL), a class of secondary metabolites. Previous studies have suggested the anti-cancer potential of Bri; however, the molecular mechanism remains elusive. The present study investigated the effects of Bri on liver cancer progression. Our findings indicated that Bri significantly suppressed the growth of liver cancer cell lines. Mechanistic researches revealed that Bri induced apoptosis through the extrinsic and intrinsic apoptotic pathways, as evidenced by the increase of Caspase-8, -9 and -3 cleavages. In addition, Bri-triggered autophagy in liver cancer cells, supported by the up-regulation of light chain 3 (LC3) II, p62, autophagy-related 5 (ATG5) and Beclin 1, as well as the occurrence of autophagic vacuoles. Importantly, Bri increased AMPK activation, while decreased the activity of its down-streaming signal, mTOR. Of note, suppression of AMP-activated protein kinase (AMPK) activation using its inhibitor, Compound C, could inhibit both apoptosis and autophagy induced by Bri. Furthermore, Bri was found to induce reactive oxygen species (ROS) generation in hepatic cancer cells. Notably, reducing ROS production by its scavenger, N-acetyl cysteine (NAC), could down-regulate p-AMPK levels, while up-regulate the phosphorylated mechanistic target of rapamycin (p-mTOR) expressions, accompanied with the restored cell viability, as well as the reduced apoptosis and autophagy in Bri-treated liver cancer cells. Finally, Bri inhibited the tumor growth in vivo without side effects. In conclusion, our study illustrated that Bri could induce apoptosis and autophagy by activating AMPK regulated by ROS in liver cancer cells, supplying molecular bases for developing Bri into an effective candidate against liver cancer.

[Clinical practice and challenges of integrative medicine in hospitals].

The clinical practice of China's integrative medicine (IM) and international integrative medicine was reviewed. As for the existent problems, we raised some personal ideas from the aspects of policies and regulations, safety, efficacy, and educational training, etc.

[Efficacy comparison between video-assisted minimally invasive radiofrequency ablation and catheter ablation in the treatment of persistent atrial fibrillation].

OBJECTIVE: To compare the efficacy of the video-assisted minimally invasive radiofrequency ablation in comparison with catheter ablation for the treatment of persistent atrial fibrillation (AF). METHODS: A total of 172 patients [116 male, mean age (56 ± 12) years] with persistent AF underwent ablation procedures during the last 4 years in our institute (83 patients underwent video-assisted minimally invasive radiofrequency ablation, group MIA and 89 patients underwent circumferential pulmonary vein linear ablation, group CA). Mean duration of preoperative AF was (72 ± 68) months. Patients were follow-uped for a period of 1 to 3.6 years [mean (2.2 ± 0.8) years]. RESULTS: There was no procedure related death. During follow-up, one patient died of encephalorrhagia in CA group, one patient died of sudden death in each group. At the end of the procedure, there were 67 sinus rhythm (39.0%), 4 pacing rhythm (2.3%), 29 atrial flutter or atrial tachycardia (16.9%) and 72 AF (41.9%). Before discharge, sinus rhythm was recorded in 53 patients (63.9%) of MIA group and in 78 patients (87.6%) of CA group; AF recorded in 24 patients (28.9%) of MIA group and in 4 patients (4.5%) of CA group (P < 0.01). At the latest follow-up, sinus rhythm was recorded in 65 patients (79.3%) of MIA group and in 54 patients (62.1%) of CA group; AF or atrial flutter was recorded in 14 patients (17.1%) of MIA group and in 24 patients (27.6%) of CA group (P = 0.028). The Kaplan-Meier survival analysis showed that the long-term efficacy of MIA is superior to CA in terms of incidence of free of AF, AF recurrence and antiarrhythmic drugs (P = 0.03, P = 0.028, P = 0.017, respectively). CONCLUSIONS: The video-assisted minimally invasive ablation was safe and effective, and had an optimistic long-term success rate for patients with long-lasting persistent AF. Thus, a randomized study comparing the long-term efficacy between the two procedures for patients with long-lasting persistent AF is warranted.

[Video-assisted minimally invasive radiofrequency ablation in the treatment of persistent atrial fibrillation].

OBJECTIVE: To evaluate the effectiveness of the video-assisted minimally invasive radiofrequency ablation combined irbesartan use for the treatment of the persistent atrial fibrillation (AF). METHODS: From January 2006 to December 2009, 83 patients with persistent AF having a video-assisted minimally invasive radiofrequency ablation. There were 58 males, 25 females with a mean age of (57 ± 11) years. Mean duration of preoperative AF was (61 ± 65) months. Follow-up for the whole patients ranged from 1.0 to 3.6 years [mean (2.2 ± 0.8) years]. Patients were randomly divided into irbesartan group (n = 42) and without irbesartan group (n = 41) postoperatively. RESULTS: No patient died postoperatively. During follow-up, there was 1 patient died of unknown reason. At the end of the procedure, 38 patients (45.7%) were sinus rhythm, 4 patients (4.9%) were pacing rhythm, 5 patients (6.0%) were atrial flutter or atrial tachycardia, and 36 patients (43.4%) were AF. Before discharge, 53 patients (63.9%) were sinus rhythm, 24 patients (28.9%) were AF. At late follow-up, 65 patients (80.2%) were sinus rhythm; 14 patients (17.3%) were AF or atrial flutter. After follow-up, the Kaplan-Meier analysis showed the irbesartan group had fewer patients with AF (P = 0.020). The hazard ratio for AF recurrence in patients treated with irbesartan was 0.24 (95% CI: 0.087 to 0.637, P = 0.004). CONCLUSIONS: The video-assisted minimally invasive radiofrequency ablation is safe and effective. The patients treated with irbesartan have a lower rate of recurrence of AF.

[Intraoperative treatment for atrial fibrillation using bi-polar radiofrequency ablation system: a clinical report of 91 cases].

OBJECTIVE: To observe the short and mid-term therapeutic effects of Bi-polar ablation systems for intraoperative treatment of atrial fibrillation (AF). METHODS: From March 2005 to January 2007, 91 patients received intraoperative treatment of atrial fibrillation with Bi-polar ablation systems, including 5 cases of paroxysmal atrial fibrillation and 86 persistent/permanent cases. The main concomitant heart diseases were rheumatic mitral valve diseases. Atricure Dry Ablation System was used for 37 cases and Cardioblate Irrigated Ablation System for 54 cases. The ablation lesion patterns included Cox-maze III, Modified Cox Mini-maze and Left-sided Maze. RESULTS: Mean ablation time was (14.1+/-6.7) min. No ablation-related complications occurred. Three patients died perioperatively. Two patients had permanent pacemaker implantation 3 months after operation. One case suffered from stroke and lower limb thrombosis 2.5 years after operation. Follow-up lasted for 6 to 29 months. The none-AF rhythm were 62.5%, 85.2%, 79.0% and 74.5% at discharge, 3 months, 6 months, and>or=12 months respectively. Compared to Uni-polar Ablation therapy group, the restoration of sinus rhythm in Bi-polar group were significantly higher at 6 months and>or=12 months postoperatively. The latest follow-up results indicated that 100% of preoperative paroxysmal atrial fibrillation patients restored sinus rhythm and 75.3% of persistent/permanent patients were free from atrial fibrillation. The none-AF rhythm of Atricure group (81.1%) showed no difference from the Cardioblate (77.5%). Meanwhile there were no significant differences among the three ablation lesion groups. CONCLUSION: Intraoperative radiofrequency ablation with Bi-polar systems is a feasible, safe and highly effective surgical option compared to the Uni-polar ablation technique.

[Video-assisted minimally invasive cardiac surgery for atrial fibrillation: a report of 57 cases].

OBJECTIVE: To evaluate the feasibility and the efficacy of a new video-assisted minimally invasive surgery for patients with atrial fibrillation (AF). METHODS: From December 2006 to October 2007, 57 patients who were 56.4 years old in average underwent the video-assisted minimally invasive cardiac operation for AF, and there were 40 male patients. Thirty-eight patients were paroxysmal AF, 7 patients were persistent and 12 patients were long-standing persistent. Three patients had failed catheter ablation, and two patients had preoperative permanent pacemaker implantation. All patients went under the minimally invasive procedure. Intraoperative electrophysiological mapping were performed. RESULTS: Mean operation time was 3.5 h. One patient was confirmed of left auricle thrombus, and one received concurrent epicardial cardiac resynchronization therapy during the procedure. There were no perioperative deaths. Acute respiratory failure occurred in 1 patient and acute heart failure in 1 patient after operation. Sixteen patients had electrical cardioversion after operation and during follow-up. At discharge, 78.9% (45/57) of all patients were in sinus rhythm (84.2% for paroxysmal AF, 71.4% for persistent AF, 66.7% for long-standing persistent AF). The patients were followed-up by 1 to 10 months. At 1 month after operation, overall 64.3% (36/56) were in sinus rhythm (67.6% for paroxysmal AF, 57.1% for persistent AF, 58.3% for long-standing persistent AF). At 3 months, overall 83.9% (47/56) were in sinus rhythm (86.5% for paroxysmal AF, 85.7% for persistent AF, 75.0% for long-standing persistent AF). At > or = 6 months, overall 87.0% (20/23) were in sinus rhythm (89.5% for paroxysmal AF, 75.0% for persistent AF). No thromboembolic event was observed during follow-up period. CONCLUSION: The video-assisted minimally invasive cardiac surgery proves to be safe, less traumatic, and presents optimistic early outcomes for paroxysmal AF patients.

[Thoracoscopy video assisted minimally invasive bilateral pulmonary vein isolation for treatment of atrial fibrillation].

OBJECTIVE: This study is to evaluate the feasibility and safety of thoracoscopy video assisted minimally invasive bilateral pulmonary vein isolation for treatment of atrial fibrillation. METHODS: From December 2006 to April 2007, thorascopy video assisted off-pump epicardial pulmonary vein isolation was performed in 20 patients with atrial fibrillation. All patients were either refractory or intolerant to antiarrhythmic drug therapy or already experienced unsuccessful catheter-based ablation. The procedure includes 21 cm ports for the thoracoscopic camera and ablation device, and a 5 cm working port on each side of the chest wall. Bilaterally pulmonary vine were isolated by using an stricure(TM) bipolar radiofrequency device. LAA was removed by using a Johnson & Johnson EZ45G stapler. Intraoperative pacing and sensing was used to confirm bidirectional block of the ablation lines. RESULTS: The procedure was successful in all patients. Nineteen patients were in sinus rhythm immediately after the surgery and 1 patient was still in AF rhythm post surgery and converted to sinus rhythm by electrical conversion in the operation room. One patient was reintubated because of low SaO2 and 1 patient received IABP for LV failure. Mean operation time was (130 +/- 25) min and average hospital stay was (8.0 +/- 3.8) d. 3-months follow up was finished in 12 patients at after the surgery and 10 patients were free of AF (10/12, 83.3%), 6-months follow up was finished in 3 patients and all in sinus rhythm (3/3, 100%). CONCLUSION: Our results suggested that thoracoscopy video assisted minimally invasive bilateral pulmonary vein isolation is a safe, feasible and effective technique for treatment of atrial fibrillation.

[Combined endocardial and epicardial radiofrequency modified Maze procedure in the treatment of atrial fibrillation].

OBJECTIVE: To evaluate the effectiveness of the combined endocardial and epicardial saline-irrigated radiofrequency modified maze procedure for the treatment of atrial fibrillation (AF). METHODS: During a period of 3 years, 295 patients with AF having concomitant cardiac surgery underwent the procedure. Patients underwent either the endocardial and epicardial group (n=185) or the endocardial group (n=110) radiofrequency ablation. There were 124 males, 171 females with a mean age of (52 +/- 11) year old. Mean duration of preoperative AF was 36 +/- 43 months. And about 90.8 percent valve pathology was rheumatic. Valve operation was performed in 289 patients, coronary artery bypass graft surgery in 19 patients and congenital heart disease operation in 6 patients respectively. Follow-up for the whole patients ranged from 3 to 47 months (mean 28 +/- 5 months). RESULTS: Ten patients died postoperatively (3.4%). Four patients died of low cardiac output, five patients died of multisystem and organ failure, one patient died of cerebral hernia. There were 2 patients died of nerves system complication during follow-up. At the end of the procedure 228 patients (77.3%) were sinus rhythm, including 78 patients (70.9%) in endocardial group while 150 patients (81.1%) in endocardial and epicardial group (P<0.05). At late follow-up, 191 of 259 patients (73.7%) were in stable sinus rhythm. Sinus rhythm was present in 64 patients (66.0%) in endocardial group while 127 patients (78.4%) in endocardial and epicardial group (P<0.05). Histopathology of the endocardial group revealed foci coagulative necrosis was limited to the endocardial side. While endocardial and epicardial ablation had full-thickness alteration of atrial tissue besides ill defined borders and inflammatory cell infiltration. CONCLUSIONS: Combined endocardial and epicardial saline-irrigated radiofrequency modified maze procedure was performed safely and efficiently. And it restored sinus rhythm better than endocardial ablation only.

Treatment of long-lasting persistent atrial fibrillation using minimally invasive surgery combined with irbesartan.

BACKGROUND: Recent studies have provided evidence that the renin-angiotensin system plays a key role in the onset and progression of atrial fibrillation (AF). The current study was designed to assess the efficacy and safety of video-assisted minimally invasive radiofrequency ablation for long-lasting persistent AF, as well as to evaluate the efficacy of the angiotensin-receptor blocker irbesartan for maintaining sinus rhythm. METHODS: Over a period of 4 years, 83 patients with long-lasting persistent AF underwent minimally invasive ablation at our center. The patients were randomly assigned to two groups, one group treated with ablation plus irbesartan, and the other with ablation alone. Follow-up ranged from 1 to 3.6 years. RESULTS: No patient died postoperatively. At the end of the procedure, 38 patients (45.7%) were in sinus rhythm, and 36 (43.4%) had AF. At the last follow-up, 65 patients (80.2%) were in sinus rhythm, 38 (92.7%) in group 1 and 27 (67.5%) in group 2 (p = 0.002). Patients in group 2 had a significantly higher rate of recurrent arrhythmia (Kaplan-Meier analysis, p = 0.004; hazard ratio, 0.24; 95% confidence interval: 0.087 to 0.637). Kaplan-Meier analysis also showed that patients treated with irbesartan had a significantly lower rate of use of antiarrhythmic drugs (p = 0.02). CONCLUSIONS: The video-assisted minimally invasive ablation procedure was safe and effective for patients with long-lasting persistent AF. Patients who were additionally treated with irbesartan had a significantly lower rate of AF recurrence than patients who were treated with ablation alone.

[Prevalence and associated factors of school physical violence behaviors among middle school students in Beijing].

OBJECTIVE: To described the prevalence of school physical violence behaviors and to explore its associated factors among middle school students in Beijing. METHODS: In 2009, a randomly selected cross-sectional survey was conducted among 5718 students in grades 7 to 12 in Beijing. A self-report anonymous questionnaire involving physical violence at school and socio-demographic variables, such as sex, grades, family economic status and family structure, peer relationships, and communication with their parents etc. were completed by students themselves. Logistic regression was used to estimate the association between physical violence and socio-demographic variables. RESULTS: Among the students, 14.3% reported that they had had physical violence behavior in school during the past 12 months. Male students had been more likely to have physical violence behaviors than female students (Male 25.2%, Female 5.1%). For both male and female students, poor school cohesion were the risk factors of physical violence behaviors (Male OR = 1.060, Female OR = 1.065). For male students, factors as father's lower education level (OR = 1.653), remarried/single-parent families (OR = 1.834), low-grade (grade 7 OR = 5.291; grade 11 OR = 1.526), poor school performance (OR = 1.470) etc were the risk factors of physical violence behaviors; while better-off family economic status (OR = 0.546), good peer relationships (OR = 0.618), and easy to communicate with the father (OR = 0.756) were the protective factors of physical violence behaviors. For female students, easy to communicate with her mother (OR = 0.358) were the protective factors of physical violence behaviors. CONCLUSION: For male and female students, the prevalence of school physical violence and its related factors were different. Actions on prevention against physical violence behaviors should be fully considered, including factors as gender, personal characteristics, family, school and peers etc.

Video-assisted minimally invasive surgery for lone atrial fibrillation: a clinical report of 81 cases.

OBJECTIVE: We sought to evaluate the feasibility and efficacy of a new type of video-assisted minimally invasive surgery for patients with atrial fibrillation. METHODS: Between December 2006 and February 2008, 81 patients with lone atrial fibrillation (49 with paroxysmal, 17 with persistent, and 15 with long-standing persistent atrial fibrillation) underwent this therapy with a bipolar radiofrequency ablation system. The main surgical procedures included bilateral pulmonary vein antrum isolation, obliteration of the left atrial appendage, division of the ligament of Marshall, and intraoperative electrophysiologic testing. RESULTS: The mean operation duration was 2.5 hours. One (1.2%) case was confirmed of left atrial appendage thrombus during the procedure. One (1.2%) patient was converted to sternotomy during the operation. Reintubation occurred in 1 (1.2%) patient, and acute heart failure occurred in 1 (1.2%) patient. One (1.2%) patient died of cerebral infarction 1 month after the operation. Follow-up was done between 3 and 19 months (mean, 12.7 +/- 3.9 months) after the operation. At discharge, 72.5% (58/81) of all patients were in sinus rhythm (paroxysmal atrial fibrillation, 83.7%; persistent atrial fibrillation, 64.7%; and long-standing persistent atrial fibrillation, 40.0%). At 3 months, overall 78.5% (62/79) were in sinus rhythm (paroxysmal atrial fibrillation, 85.7%; persistent atrial fibrillation, 82.4%; and long-standing persistent atrial fibrillation, 46.2%). At 6 months, overall 78.5% (62/79) were in sinus rhythm (paroxysmal atrial fibrillation, 85.7%; persistent atrial fibrillation, 70.6%; and long-standing persistent atrial fibrillation, 61.5%). At 12 months, overall 79.6% (39/49) were in sinus rhythm (paroxysmal atrial fibrillation, 80.0%; persistent atrial fibrillation, 75.0%; and long-standing persistent atrial fibrillation, 66.7%). At 18 months, 88.9% (8/9) of the paroxysmal group were in sinus rhythm. CONCLUSIONS: This minimally invasive technique proves to be safe and less traumatic and presents optimistic early outcomes for patients with paroxysmal and persistent atrial fibrillation. It might find wider application if more ablation lesions could be enrolled for long-standing persistent atrial fibrillation.

Intraoperative modified Cox mini-maze procedure for long-standing persistent atrial fibrillation.

BACKGROUND: As the most effective method of curing atrial fibrillation, the classic Maze III procedure eliminates atrial fibrillation in more than 90% of patients. In spite of high efficacy, the complexity and complications associated with this procedure prevents widespread application. In this research, we report our experience with a modified Cox mini-Maze procedure using radiofrequency energy for treating long-standing persistent atrial fibrillation during open-heart surgery. METHODS: A total of 45 patients with long-standing persistent atrial fibrillation who underwent open-heart surgery received the treatment. This modified Cox mini-Maze procedure was performed using unipolar and bipolar radiofrequency systems. Some lesions were done with unipolar pen both epicardially and endocardially to improve the transmurality of ablation. RESULTS: Hospital mortality was 0%. The follow-up time ranged from 6 to 26 months (mean, 16.6). Overall freedom from atrial fibrillation was 86.7% at latest follow-up after surgery. When analyzed by the Kaplan-Meier method, freedom from atrial fibrillation was 94% (6 months), 87% (12 months), and 82% (24 months). Compared with a randomized Cox Maze III control group, the results of freedom from atrial fibrillation do not show significant differences between the two groups at interval contacts. The survival rate was 100% (45 of 45), as was freedom from stroke. No patients required implantation of a permanent pacemaker. Recovery of atrial contractility occurred in 94.6% of patients (35 of 37) during the latest follow-up. CONCLUSIONS: According to our experience, the modified Cox mini-Maze procedure allows rapid ablation application and offers an optimistic outcome for the recovery of sinus rhythm in patients with long-standing persistent atrial fibrillation who undergo open-heart surgery.