Overexpression of close homolog of L1 enhances the chemosensitivity of lung cancer cells via inhibition of the Akt pathway.

Drug resistance leads to tumor relapse and further progression during chemotherapy in lung cancer. Close homolog of L1 (CHL1) has been identified as a tumor suppressor in most malignancies. However, to the best of our knowledge, whether CHL1 mediates chemoresistance remains unknown. The present study observed that CHL1 was significantly downregulated in cisplatin (DDP)-resistant cells (A549/DDP) and paclitaxel (PTX)-resistant cells (A549/PTX) compared with A549 cells. When treated with or without DDP and PTX, silencing of CHL1 in A549 cells promoted the cell survival rate and clone formation, and decreased apoptosis. Whereas overexpression of CHL1 in A549/DDP and A549/PTX cells impeded the cell survival and clone formation and promoted apoptosis. Additionally, CHL1 overexpression enhanced the chemosensitivity of A549/DDP cells to DDP in vivo. Notably, the chemoresistance induced by CHL1 depletion was reversed by the Akt inhibitor SC66 in A549 cells. The results of the present study demonstrated that CHL1 enhanced sensitivity of lung cancer cells by suppressing the Akt pathway, which suggested that CHL1 may be a potential target for overcoming chemoresistance in lung cancer.

MiR-31 promotes Th22 differentiation through targeting Bach2 in coronary heart disease.

The aim of the present study was to investigate the role of miR-31 in Th22 differentiation in coronary heart disease (CHD). Th22 frequencies in peripheral blood of CHD patients and controls as well as in CD4+ T cells were detected by flow cytometry. The mRNA expression of Th22-associated transcription factor aryl hydrocarbon receptor (AHR) and Th22-effector cytokine interleukin (IL)-22, as well as miR-31 were examined by quantitative real-time PCR (qRT-PCR). The protein level of BTB domain and CNC homolog 2 (Bach2) was measured by Western blotting. The interaction between miR-31 and Bach2 was verified using dual luciferase reporter assay. The results showed that Th22 frequency and miR-31 expression were elevated in CHD patients. Furthermore, miR-31 mimic and Bach2 silencing significantly promoted Th22 frequency and the levels of AHR and IL-22 in CD4+ T cells from CHD patients. Further studies showed that miR-31 facilitated Th22 cell differentiation by targeting and inhibiting Bach2. Our data indicate that miR-31 promotes Th22 differentiation through targeting Bach2 in CHD.

[Protective effect of right coronary artery ischemic preconditioning on myocardial ischemia reperfusion injury in rabbit heart].

OBJECTIVE: To explore the protective effects of right coronary artery ischemic preconditioning and post-conditioning on myocardial ischemia reperfusion injury in rabbit heart.
 Methods: A total of 30 rabbits were randomly divided into 4 groups: a control group (n=7), an ischemia reperfusion group (IR group, n=8), an ischemic preconditioning group (IPC group, n=8) and an ischemic post-conditioning group (IPO group, n=7). Venous blood samples were taken at pre-operation, 1 and 6 h post-operation, and the concentration of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin-T (cTn-T) were measured. The infarct area of cardiac muscle was calculated.
 Results: Compared with the IR group, the levels of CK-MB and cTn-T at 1 and 6 h post-operation in the IPC group and the IPO group were reduced (all P<0.05). Compared with the IR group, the infarct size in the IPC group and the IPO group was significantly decreased, with significant difference (both P<0.05) .
 Conclusion: Right coronary artery ischemic preconditioning and post-conditioning exert significant protective effects on the myocardial ischemia reperfusion injury in New Zealand rabbits.

Apoptosis-related microRNA changes in the right atrium induced by remote ischemic perconditioning during valve replacement surgery.

We previously found that remote ischemic perconditioning (RIPerc) was effective in attenuating myocardial injury during cardiac surgery. Given that microRNAs (miRs) act as an important player in ischemic/reperfusion (I/R) injury and apoptosis, this study aimed to investigate whether RIPerc reduces apoptosis in atrial myocardium and which apoptosis-related miRs are involved during valve replacement surgery. Here, we demonstrated that RIPerc inhibited apoptosis in atrial myocardium during cardiac ischemia and that 17 miRs showed at least a 1.5-fold change in expression after ischemia. Of the 17 miRs, 9 miRs, including miR-1, miR-21, miR-24, and miR-195, which are related to apoptosis, exhibited different expression patterns in the RIPerc group compared with the control. Using qRT-PCR and Western blotting, we demonstrated that miR-1 and miR-195 were downregulated and that their common putative target gene Bcl-2 was upregulated in the RIPerc group. However, the differences in miR-21 and miR-24 expression, together with programmed cell death 4 (PDCD4), which is the target gene of miR-21, were not significant. These findings provide some insight into the role of miRs in the cardioprotective effects induced by RIPerc.

Ischemic postconditioning altered microRNAs in human valve replacement.

BACKGROUND: Although the involvement of microRNAs (miRNAs) has been intensively studied in myocardial infarction, there is no report on the regulation of miRNAs by ischemic postconditioning in patients undergoing cardiac surgery. We aim to explore the regulation of miRNAs by ischemic postconditioning in double valve replacement. MATERIALS AND METHODS: In this prospective, controlled clinical study, consecutive 30 patients undergoing double valve replacement were enrolled. The patients were randomized into two groups, namely an ischemic postconditioning (IPO) group (n = 15) and a control (CON) group (n = 15). For ethical considerations, samples of right atrial muscle were harvested, respectively, 10 min before cardiopulmonary bypass (pre-CPB) and 5 min after aortic declamping (post-CPB) for analysis of miRNAs, genes and apoptosis. RESULTS: Compared with the CON group, miR-1 was downregulated, whereas miR-21 was upregulated, and BCL2 messenger RNA (mRNA) was upregulated, whereas BAX mRNA and programmed cell death 4 mRNA remained unchanged in the IPO group. Likewise, a significant increase in BCL2 protein and a striking decrease in BAX protein were observed in the IPO group when compared with those in the CON group. The IPO group showed a significantly smaller increase of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive myocytes after CPB than CON group. CONCLUSIONS: Ischemic postconditioning could regulate miR-1, miR-21, and downstream effectors and resulted in actual attenuation of apoptosis in patients undergoing valvular heart surgery.

Multiorgan protection of remote ischemic perconditioning in valve replacement surgery.

BACKGROUND: Remote ischemic perconditioning (RIPerc) is a new alternative of remote ischemic conditioning and has not been well studied. RIPerc attenuates myocardial injury when applied during cardiac surgery. However, its protective effects on other organs remain unknown. MATERIALS AND METHODS: Patients with rheumatic heart disease undergoing valve replacement surgery were randomized into the RIPerc group (n = 101) or the control group (n = 100). RIPerc was achieved by three cycles of 5-min ischemia-5-min reperfusion in the right thigh during surgery. Clinical data and the levels of injury biomarkers for the heart, lungs, liver, and kidneys within 48 h after surgery were compared using one-way or repeated measurement analysis of variance. RESULTS: In the RIPerc group, the release of serum cardiac troponin I (128.68 ± 102.56 versus 172.33 ± 184.38, P = 0.04) and the inotropic score (96.4 ± 73.8 versus 121.5 ± 89.6, P = 0.032) decreased compared with that of the control; postoperative drainage (458.2 ± 264.2 versus 545.1 ± 349.0 ml, P = 0.048) and the incidence of acute lung injury was reduced (36.6% versus 51%, P = 0.04), and the extent of hyperbilirubinemia was also attenuated. No significant difference was observed in the levels of biomarkers for renal injury and systemic inflammation response. CONCLUSIONS: RIPerc applied during the valve replacement surgery induced multiple beneficial effects postoperatively including reduced drainage and myocardial damage, lower incidence of acute lung injury, and attenuated hyperbilirubinemia.

Simple random sampling-based probe station selection for fault detection in wireless sensor networks.

Fault detection for wireless sensor networks (WSNs) has been studied intensively in recent years. Most existing works statically choose the manager nodes as probe stations and probe the network at a fixed frequency. This straightforward solution leads however to several deficiencies. Firstly, by only assigning the fault detection task to the manager node the whole network is out of balance, and this quickly overloads the already heavily burdened manager node, which in turn ultimately shortens the lifetime of the whole network. Secondly, probing with a fixed frequency often generates too much useless network traffic, which results in a waste of the limited network energy. Thirdly, the traditional algorithm for choosing a probing node is too complicated to be used in energy-critical wireless sensor networks. In this paper, we study the distribution characters of the fault nodes in wireless sensor networks, validate the Pareto principle that a small number of clusters contain most of the faults. We then present a Simple Random Sampling-based algorithm to dynamic choose sensor nodes as probe stations. A dynamic adjusting rule for probing frequency is also proposed to reduce the number of useless probing packets. The simulation experiments demonstrate that the algorithm and adjusting rule we present can effectively prolong the lifetime of a wireless sensor network without decreasing the fault detected rate.

A comparison of cardiac post-conditioning and remote pre-conditioning in paediatric cardiac surgery.

BACKGROUND: Remote ischaemic pre-conditioning and cardiac ischaemic post-conditioning provide myocardial protection in cardiac surgery. However, these two endogenous strategies have not been directly compared in a clinical setting. The purpose of this study was to compare the efficacy of remote ischaemic pre-conditioning and post-conditioning in providing myocardial protection to children undergoing cardiopulmonary bypass for surgical repair of ventricular septal defect. METHODS: We randomly assigned 60 paediatric patients scheduled for surgical correction of congenital ventricular septal defect to the post-conditioning group (n = 20), remote pre-conditioning group (n = 20), or control group (n = 20). Post-conditioning consisted of 30 seconds of ischaemia and 30 seconds of reperfusion achieved by clamping and unclamping the aorta, repeated three times over 3 minutes immediately after cardioplegic arrest. Remote ischaemic pre-conditioning consisted of 5 minutes of lower limb ischaemia followed by 5 minutes of reperfusion using a blood-pressure cuff inflated to a pressure of 200 millimetres of mercury, also repeated three times over 30 minutes. We assayed creatine kinase-MB, troponin I. RESULTS: Mean age, cardiopulmonary bypass times, and aortic cross-clamp times were matched across groups. Both post-conditioning and remote ischaemic pre-conditioning reduced the peak release of creatine kinase-MB (86.1 plus or minus 24.1 units per litre and 92.8 plus or minus 20.6 units per litre, respectively, versus 111.0 plus or minus 44.6 units per litre in the control, p less than 0.05) and troponin I (0.28 plus or minus 0.10 nanogram per millilitre and 0.26 plus or minus 0.09 nanogram per millilitre, respectively, versus 0.49 plus or minus 0.19 nanogram per millilitre in the control group, p less than 0.05). CONCLUSIONS: Our study demonstrates that ischaemic post-conditioning and remote ischaemic pre-conditioning provide comparable myocardial benefit in children undergoing cold blood cardioplegic arrest.

[Protective effect of aminophylline on cerebral injury during cardiopulmonary bypass in infants].

OBJECTIVE: To investigate the protective effect of aminophylline on cerebral injury induced by cardiopulmonary bypass (CPB) in infants. METHODS: Forty patients who underwent ventricular septal defect within 3 years old were randomly divided into 2 groups(20 cases in each group).Aminophylline group:aminophylline (5 mg/kg) was injected slowly via the vein after anesthesia and maintained at a dose of 0.5 mg/(kg.h) until the end of CPB. CONTROL GROUP: aminophylline was replaced by Ringer's lactated solution. Samples were obtained at the beginning of CPB (T(1)),the end of CPB (T(2)),6 h (T(3)) and 24 h (T(4)) after the operation to measure S-100 beta protein, NSE, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and interleukin-10 (IL-10) concentration by ELISA in the 2 groups. RESULTS: Compared with the time point immediately before CPB, the S-100beta protein,NSE, TNF-alpha, and IL-8 concentration in the 2 groups began to increase with the start of CPB, reached a climax at the end of CPB (T(2)),decreased gradually 6 h after the termination of CPB(T(3)) and could not restore to the level before CPB at T(4)(24 h after the termination of CPB).IL-10 in the 2 groups both increased after the CPB. At T(2) and T(3), S-100beta protein,NSE, TNF-alpha, and IL-8 concentrations were significantly lower than those in the aminophylline group (P<0.05 or P<0.01), while IL-10 was just the opposite. CONCLUSION: There is cerebral damage induced by CPB. Aminophylline may play a protective role in cerebral injury by modulating the balance between the pro-inflammatory factor and anti-inflammatory factor to reduce the level of S-100beta protein and NSE during CPB and open cardiac surgeries.

[Cardiopulmonary protection of ischemic postconditioning in cardiac surgery in children with tetralogy of Fallot].

OBJECTIVE: Ischemic postconditioning effectively minimizes the ischemic/reperfusion injury, and the large series of case reports on its protective effects in cardiac surgery are limited. A randomized trial was conducted to investigate the effect of ischemic postconditioning on cardiopulmonary protection in children undergoing cardiac surgery for tetralogy of Fallot. METHODS: One hundred and five-children with tetralogy of Fallot undergoing surgery were randomly assigned to control (n=58) and ischemic postconditioning groups (n=47). Ischemic postconditioning was performed by intermittent aortic clamping after reperfusion. After surgery, the duration of intensive care unit (ICU) stay, capacity of blood transfusion, hemodynamics, inotropic scores, respiratory function, and release of blood lactate were assayed. RESULTS: There was a significant decrease in the ICU stay in the postconditioned group compared with the control group (37+/-21 hrs vs 54+/-26 hrs; P<0.05 ). The capacity of blood transfusion (308+/-230 mL vs 526+/-515 mL; P<0.05) and the inotropic scores (5.9+/-5.0 vs 10.3+/-7.7; P<0.05) in the postconditioned group were significantly reduced compared with those in the control group. Blood lactate contents in the postconditioned group was significantly lower that those in the control group 1, 3, 6, 9, 12 and 20 hrs after surgery. The postconditioned group showed more improved hemodynamics and respiratory function than the control group. CONCLUSIONS: Ischemic postconditioning may provide clinical benefits with respects to myocardial and pulmonary protections in children undergoing repair for tetralogy of Fallot.

Clinical benefit of cardiac ischemic postconditioning in corrections of tetralogy of Fallot.

The postoperative course of cyanotic patients is generally more complicated than in acyanotic patients. The ischemic postconditioning provides protection from myocardial injury. We conducted a randomized trial to evaluate the clinical benefits of postconditioning in patients undergoing repair of tetralogy of Fallot. Ninety-nine patients with tetralogy of Fallot were randomly assigned to ischemic postconditioning group (n=48) or control group (n=51). The postconditioning was performed by intermittent aortic clamping after reperfusion. The morbidity, mortality, ventilation time, length of ICU stay, inotropic score, release of troponin I and lactate were assayed. There was one death in postconditioned group and two in control. Major non-fatal morbidity was reduced in postconditioned patients (12.5%, 6/48) compared with control (33.3%, 17/51, P=0.016). The troponin I was significantly lower (P=0.026) with reduced inotrope score (P=0.001) and lactate release (P=0.019) in postconditioned patients. The ventilation time was significantly reduced in postconditioned patients compared with control (14+/-15 h vs. 25+/-28 h, P=0.024). There was a significant decrease in the ICU stay in the postconditioned patients (P=0.048). The study suggests that ischemic postconditioning may provide clinical benefits with respect to the morbidity, ventilation time, ICU stay, requirement of inotrope in patients undergoing repair for tetralogy of Fallot.

Does cardioplegia leave room for postconditioning in paediatric cardiac surgery?

BACKGROUND: Postconditioning by brief episodes of ischaemia performed just at the time of reperfusion have been shown to reduce the size of infarcts in animal models, and in the clinical setting of percutaneous cardiac intervention. The clinical applicability of postconditioning in cardiac surgery remains to be determined. We investigated the effect of postconditioning on myocardial protection in children undergoing cardiac surgery. METHODS: We randomly assigned 40 patients scheduled for surgical correction of congenitally malformed hearts under cold blood cardioplegic arrest to postconditioning or control treatment. Postconditioning was performed by two cycles of 30 seconds ischaemia and 30 seconds reperfusion using aortic reclamping, and declamping started 30 seconds after cardioplegic arrest. We assayed creatine kinase-MB, troponin I, transcardiac release of lactate and neutrophil counts. RESULTS: The types of procedure, age, bypass and aortic cross-clamping times were similar in both groups. The postoperative peaks of creatine kinase-MB and troponin I were lower after aortic de-clamping in the postconditioned patients compared with their controls (128 +/- 48 units per liter as opposed to 199 +/- 79 units per liter, p = 0.016, and 0.34 +/- 0.21 nanograms per milliliter as opposed to 0.61 +/- 0.53 nanograms per milliliter, p = 0.05), with reduced inotropic scores in those submitted to postconditioning compared with their controls (4.8 +/- 3.1 versus 2.3 +/- 1.5, p = 0.036). Transcardiac release of lactate was reduced in the postconditioned patients compared with their controls (0.10 +/- 0.27 as opposed to 0.37 +/- 0.43 millimols per liter, p = 0.048). No differences between groups were found for transcardiac neutrophil count during reperfusion (10.8 +/- 6.3% for postconditioning versus 14.0 +/- 8.7% for controls, p = 0.48). CONCLUSIONS: Our study demonstrates that postconditioning may protect the myocardium of children undergoing cold blood cardioplegic arrest. These data support the need for a larger clinical trial of postconditiong in children undergoing cardiac surgery.

Right coronary artery translocation in tetralogy of Fallot.

We describe a simple and cost-effective technique to repair anomalous origin of the right coronary artery from the left coronary artery in tetralogy of Fallot. The proximal right coronary artery is re-implanted into the aorta after it is mobilized and transected. This technique avoids the use of conduits in infants or adults with tetralogy of Fallot and anomalous right coronary arteries, and maintains the growth potential of the translocated native coronary artery.

Effect of ischemic postconditioning in adult valve replacement.

OBJECTIVE: Ischemic postconditioning (POC) by brief episodes of ischemia performed just at the time of reperfusion can reduce infarct size in animal models and clinical settings of percutaneous coronary intervention. However, the clinical applicability of postconditioning in cardiac surgery remains to be determined. We investigated the effect of postconditioning on myocardial protection in patients undergoing valve replacement. METHODS: Fifty adult patients scheduled for elective valve replacement under cold blood cardioplegic arrest were randomly assigned to postconditioning (n=25) or control treatment (n=25). Postconditioning was performed by three cycles of 30s ischemia and 30s reperfusion using aortic re-clamping and de-clamping started 30s after cardioplegic arrest. The creatine kinase-MB, troponin I, transcardiac release of lactate were assayed. Measurements of clinical results were recorded during the study. RESULTS: The types of procedure, age, bypass and aortic cross-clamping times were similar in both groups. The postoperative peak creatine kinase-MB was lower after aortic de-clamping in the postconditioning patients compared with the control group (66+/-24 U/l vs 84+/-20 U/l, p=0.02) and peak cTnI was similar in both groups. The required inotropes were reduced in postconditioning group compared with the control group (2.3+/-1.8 vs 4.1+/-2.2 microg/min/kg, p=0.03). There were reduction trends with regard to transcardiac release of lactate in postconditioning group compared with the control group (0.10+/-0.17 mmol/l vs 0.24+/-0.16 mmol/l, p=0.08). The transcardiac neutrophil count during reperfusion was less in POC group compared with the control group (7.8+/-6.3% vs 14.0+/-8.7%, p=0.04). CONCLUSIONS: The present study demonstrated that postconditioning may protect adult myocardium undergoing cold blood cardioplegic arrest. These data support the need for a further clinical trial of postconditioning in cardiac surgery.

[Mechanical valve replacement in children with heart valve diseases].

OBJECTIVE: To determine the surgical point and technique of artificial mechanical valve replacement in children with heart valve diseases. METHODS: From Jan. 1989 to Oct. 2005, 63 children under 15 years received mechanical cardiac valve replacement with cardiopulmonary bypass (CPB). RESULTS: The valve replacement included aortic valve replacement in 20 children, mitral valve replacement in 37 children and combined aortic valve and mitral valve replacement in 6 children. CONCLUSION: The operation mortality was 7.94%(5/63). The follow-up periods were from 4 months to 204 months. The late mortality was 10.34%(6/58). All the other children were in NYHA class I - II. The operation mortality of children with heart valve replacement is higher than that of adults, but it was very effective.

Effects of aminophylline on cytokines and pulmonary function in patients undergoing valve replacement.

OBJECTIVE: This study is to evaluate the effects of aminophylline on systemic inflammatory response after cardiopulmonary bypass in patients undergoing valve replacement. METHODS: Thirty patients undergoing elective valve replacement were randomized to receive either aminophylline treatment (aminophylline, n = 15) or no aminophylline (control, n = 15). Administration of aminophylline (5 mg/kg) was injected intravenously after induction of anesthesia and maintained with 0.5 mg/kg per h until the end of cardiopulmonary bypass. Perioperative cytokines (interleukin-8 and interleukin-10, tumor necrosis factor-alpha) and respiratory function, blood neutrophil count ratio of right atrium to that of left atrium, plasma malondialdehyde were measured during the experiment. RESULTS: Interleukin-8 and tumor necrosis factor-alpha levels after cardiopulmonary bypass were significantly lower in the aminophylline group than that in the control group (P < 0.05, for each group), and interleukin-10 level in aminophylline group was significantly higher than in control (P = 0.001). The respiratory index was greater in the control than in aminophylline group (P < 0.05). Neutrophil count ratio of right atrium blood to left atrium blood and plasma malondialdehyde level in aminophylline group were much lower (P = 0.02 and 0.001, respectively) than in the control 30 min after aortic declamping. Compared with control group, the duration of ventilation and intensive care unit stays were shorter in aminophylline group (P = 0.032 and 0.013, respectively). CONCLUSIONS: Intraoperative administration of aminophylline had anti-inflammatory effect and improved pulmonary oxygenation in patients undergoing valve replacement.