Mendelian randomization study of IGF-1, childhood obesity and obesity-related asthma.

Insulin-like growth factor 1 (IGF-1) has been reported to potentially link with childhood obesity and obesity-related asthma, although a causal effect has not been illustrated. This study aimed to assess their association via multi-variable Mendelian randomization (MR) analysis with two-sample summary-level data on genetic variants as instrumental variables, thus estimating a causal effect. Genetic variants associated with serum IGF-1 at genome-wide significance (GWS) in the UK Biobank study involving 363,228 individuals of European descent were introduced as instrumental variables. Summary-level data on childhood obesity and obesity-related asthma were obtained from genome-wide association studies (GWAS). Here, MR-Egger, inverse-variance weighted (IVW), simple median, weighted median and penalized weighted median methods were used in the MR study. Results showed that there were strong causal associations of IGF-1 with childhood obesity (OR, 1.27; 95% CI 1.01-1.60; P<0.05) and obesity-related asthma (OR, 1.22; 95% CI 1.07-1.38; P<0.005). In conclusion, A causal association between high IGF-1 levels and high risks of childhood obesity and obesity-related asthma is estimated, which requires further validation in large-scale trials.

Perioperative Brain Injury in Children with Aortic Arch Anomalies: A Retrospective Study of Risk Factors and Outcomes.

Complex pediatric cardiac disease is associated with brain impairment and neurodevelopmental disorders, particularly in patients requiring cardiac surgery for aortic arch anomalies. This study examines the incidence, risk factors, and outcomes of perioperative brain injury in children undergoing aortic arch repair who had aortic arch anomalies. A total of 145 children with aortic arch anomalies in our center undergoing aortic arch repair between January 2014 and December 2022 were enrolled. There were 129 (89.0%) with coarctation of the aorta (COA) and 16 (9.7%) with interrupted aortic arch (IAA). Risk factor analysis of brain injuries was done using perioperative imaging and included symptoms of hemorrhagic stroke, arterial ischemic stroke, white matter injury, cerebral sinus venous thrombosis, and other pathologies. Preoperatively, 50/145 (34.5%) patients had brain injuries. Multivariate analysis showed that an increased risk of hemorrhagic stroke was associated with newborns (odds ratio [OR], 2.09 [95% CI 0.08-3.50]), isolated COA (OR, 3.69 [95% CI 1.23-7.07]), mechanical ventilation (MV) ([OR, 2.56 [95% CI 1.25-4.03]), and sepsis (OR, 1.73 [95% CI 0.46-3.22]). Newborns ([OR, 1.91 [95% Cl 0.58-3.29]) and weight-for-age z score ([OR, -0.45 [95% CI -0.88 to -0.1]) were associated with an increased risk of white matter injury. New postoperative brain injuries were present in 12.9% of the patients (16/124). Deep hypothermic circulatory arrest (DHCA) was associated with new postoperative brain injuries compared with deep hypothermic low-flow (DHLF) plus antegrade cerebral perfusion (ACP) (([OR, 2.67 [95% CI, 0.58-5.75])). Isolated COA was almost associated with new postoperative brain injuries (OR, 1.13 [95% CI, -0.04 to 2.32]). Children diagnosed with isolated COA appeared to have a higher risk of perioperative brain injury, but the underlying mechanisms are still unclear. We focused on the intrinsic mechanism by which changes in hemodynamics caused by COA result in perioperative brain injury. Further research will be needed to optimize the personalized treatment and cerebral perfusion techniques for complex pediatric cardiac surgery.

Long-term outcomes in children undergoing vascular ring division: a multi-institution experience.

OBJECTIVES: Vascular rings are rare anomalies of congenital heart disease that cause respiratory and gastrointestinal symptoms. This study assessed the long-term outcomes of patients with vascular ring division. METHODS: A multi-institution retrospective review of 371 patients with vascular rings undergoing surgical division at 3 paediatric cardiac institutions between November 2007 and October 2019 was performed. RESULTS: The complete vascular rings consisted of a double aortic arch (24.5%), right aortic arch with left ligamentum arteriosum (36.7%) and left aortic arch, with right ligamentum arteriosum (0.5%). The incomplete vascular rings consisted of a pulmonary artery sling (22.9%), left aortic arch with aberrant right subclavian artery (15.1%) and innominate artery compression syndrome (0.3%). Respiratory symptoms included stridor (71.4%), wheezing (49.1%), coughing (31.5%), gastrointestinal symptoms included choking (12.4%), dysphagia (3.2%) and emesis (1.9%). Only one patient died after discharge, yielding a late mortality rate of 0.3% (1/360). The 10-year overall survival rate was 96.8%. Postoperative complications were reported in 51 patients, 15 of whom required reoperation. The 10-year freedom from reoperation rate was 95.9%. Follow-up was completed in 95.4% (354/371) of patients, with a mean follow-up time of 4.3 ± 2.9 years (range from 1 to 13 years). Twenty patients (5.6%) experienced residual symptoms during long-term follow-up. CONCLUSIONS: The outcomes of vascular ring division are excellent. A Kommerell diverticulum >1.5 times the aberrant left subclavian artery origin is an operative indication for primary resection. Tracheomalacia is a risk factor for reoperation and residual symptoms, and preoperative fibrobronchoscopy is important for evaluation.

Serum vitamin E concentration is negatively associated with body mass index change in girls not boys during adolescence.

BACKGROUND: Vitamin E is the most abundant lipid-soluble antioxidants present in plasma; however, the relationship between serum vitamin E and change in body mass index (BMI)-for-age Z scores in adolescents has not been well described. METHODS: This study is a cross-sectional study. Data were analyzed from 4014 adolescents who participated in the National Health and Nutrition Examination Survey. The nutritional status was calculated by BMI Z scores and was classified into normal weight, overweight, and obese. Multivariable-adjusted logistic regression was used to examine the association between serum vitamin E levels with overweight/obesity. Besides, the interaction effects between potential confounders and vitamin E on obesity were further evaluated. RESULTS: After adjusting potential confounders, serum vitamin E levels were negatively associated with overweight/obesity in girls but not in boys. Per standard deviation increment in vitamin E concentrations was associated with a 92% decreased risk of obesity in females. Besides, lower quartiles of serum vitamin E were associated with a higher risk of overweight/obesity in girls. Moreover, the inverse association between serum vitamin E levels and obesity was also found in most subgroups through subgroup analysis. CONCLUSIONS: Our study supports the negative association between serum vitamin E levels and overweight/obesity in adolescents. A higher serum vitamin E level may be associated with a reduced probability of obesity in girls, but not in boys.

Clinical characteristics and risk factors of fatal patients with COVID-19: a retrospective cohort study in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. METHODS: In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. RESULTS: Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. CONCLUSIONS: The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.

Inflammatory Myofibroblastic Tumors in Children: A Clinical Retrospective Study on 19 Cases.

Background: Inflammatory myofibroblastic tumor (IMFT) is a rare neoplasm mainly affecting children and young adults. We conducted a retrospective study to evaluate the clinical features and treatment alternatives of childhood inflammatory myofibroblastic tumors. Methods: A total of 19 patients who were pathologically diagnosed with IMT between December 2008 and October 2018 were included. Collected data were demographic information, main complaints, tumor characteristics, treatment, pathological results, immunohistochemical analysis, and prognosis. Results: The male/female ratio was 13:6. The mean age at disease onset was 44.9 ± 33.9 months (range 4 to 111 months). The mean tumor size was 6.5 ± 4.0 cm (range 1.2 to 17.0 cm). The most common site was the abdomen (13/19). The most commonly used detection tool was CT. Eleven patients (57.9%) had aggressive tumor growth, including eight receiving extensive resection and three receiving palliative resection due to high local invasiveness and postoperative chemotherapy. Eight cases whose tumors were completely enveloped received complete resection. Immunohistochemistry was performed for 17 patients and ALK positivity was found in 11 patients. Despite three children lost to follow-up, sixteen patients were followed up for 6 to 132 months (average 63.9 months, median 66 months). Of which, twelve children survived with no evidence of IMT, and four cases (21%) showed local recurrences (two of them died). No distant metastasis was detected. Conclusions: IMT is rare in children with various locations, mostly appearing in the abdomen. Whether the tumor could be completely removed, the location and the invasiveness of surrounding tissues might be highly prognosis-related.

Clinical Treatment of Pediatric Primary Cardiac Tumors: A Single-Institute 12-Year Experience.

BACKGROUND: Primary cardiac tumors in children are extremely rare. This study aimed to analyze clinical treatment and follow-up of pediatric primary cardiac tumors. PATIENTS AND METHODS: We performed a retrospective analysis by searching the medical records of 75 patients diagnosed with pediatric primary cardiac tumors from June 2005 to August 2017 in our institution. We followed operative patients every half year in the first postoperative year and then at least every year. If the patients had no serious symptoms or hemodynamic changes, they received nonoperative management and were followed regularly every year. RESULTS: Nineteen patients underwent surgery at our department for serious symptoms and critical hemodynamic changes. Four patients had postoperative complications. Two died of low cardiac output syndrome and arrhythmia after surgery. One patient with myxomas had tumor recurrence and one had been found of another rhabdomyoma after surgery. The other 14 patients recovered well. Fifty-six patients had nonoperative management. Four were lost in follow-up. Two patients with malignant tumors died of unknown causes after discharge. The remaining patients had no severe symptoms or tumor growth during follow-up. CONCLUSIONS: Clinical treatment of pediatric primary cardiac tumors should be performed individually. Most pediatric primary cardiac tumors are benign, and spontaneous regression is possible, especially for rhabdomyomas. The principle purpose of surgical treatment is to restore normal hemodynamics and protect important structures and cardiac tissue.

Comparison of efficacy between video-assisted thoracoscopic surgery and thoracotomy in children with mediastinal tumors: 6-year experience.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been increasingly used in pediatric patients. We evaluated the outcomes of VATS and thoracotomy for pediatric mediastinal tumors. METHODS: A total of 137 patients who underwent surgery for mediastinal tumors at our department from March 2012 to September 2018 were recruited in this retrospective study. Forty-three patients were treated by VATS and ninety-four underwent thoracotomy (two patients who underwent open surgery were excluded from the study because they were lost to follow-up). Data including demographic information, tumor characteristics, operative time, conversion of surgery, blood transfusion, postoperative hospital stay, mortality and recurrence were collected and compared between the two groups. RESULTS: No significant difference was found in gender, age, weight and tumor distribution between the two groups. The number of patients with malignant tumors who underwent thoracotomy was significantly higher than those who received VATS (78.0% vs. 22.0%, P=0.04). Patients received thoracotomy had significantly larger mean tumor diameter than those who underwent VATS (7.6±3.8 vs. 4.4±1.7 cm, P<0.001). The intraoperative transfusion rate in the thoracotomy group was significantly higher than that in the VATS group (67.4% vs. 14.0%, P<0.001), so was the amount of blood transfusion (148.1±150.7 vs. 23.3±61.1 mL, P<0.001). The VATS group had significantly shorter operative time as compared with the thoracotomy group (94.3±40.9 vs. 133.5±72.1 min, P=0.002). During follow-up, local recurrence was found in 8 (8.7%) patients who underwent thoracotomy, and no significant difference was found in local recurrence rate between the two groups. Four patients who underwent thoracotomy died, and no significant difference was found in mortality between two groups. CONCLUSIONS: Due to less blood transfusion, shorter operative time and postoperative hospital stay, VATS is a safer surgical treatment for pediatric mediastinal tumors than thoracotomy.

[Application of thoracoscopic surgery in repairing esophageal atresia type â ¢ with tracheoesophageal fistula in neonates].

OBJECTIVE: To compare the efficacy of thoracoscopic surgery versus thoracotomy in repairing esophageal atresia type Ⅲ with tracheoesophageal fistula (EA/TEF) in neonates. METHODS: A retrospective analysis was conducted in 97 neonates who underwent EA/TEF repair between January 2012 and December 2017 in the Affiliated Children's Hospital of Nanjing Medical University, including 75 patients receiving thoracotomy and 22 patients receiving thoracoscopic surgery. The perioperative data and the incidence of early postoperative complications were compared between two groups. RESULTS: The operations were completed in all patients. One child (4.5%) in thoracoscopic surgery group was converted to thoracotomy with modified Livaditis procedure due to the long distance of two blind ends (>4 cm) and thinner distal end. The operation time was longer in thoracoscopic surgery group[(143±48) min vs. (120±40) min, P<0.05], but the postoperative ventilation time was shorter[(55±22) h vs. (65±19) h, P<0.05] and the first oral feeding was earlier in thoracoscopic surgery group[(3.2±1.1) d vs (3.9±1.3) d, P<0.05]. No statistical difference was observed in the ratio of red blood cell transfusion, length of hospital stay and drainage tube indwelling time between two groups (all P>0.05). The incidence of lung complications in thoracotomy group was higher than that in thoracoscopic surgery group (20.0% vs. 9.1%, P<0.01), while there were no significant differences in the incidence of other postoperative complications between two groups. There was no death in thoracoscopic surgery group, while 2 patients died in thoracotomy group. CONCLUSIONS: Thoracoscopic repair is a preferred surgical procedure for EA/TEF in neonates.

Whole-exome sequencing identifies SGCD and ACVRL1 mutations associated with total anomalous pulmonary venous return (TAPVR) in Chinese population.

As a rare type of Congenital Heart Defects (CHD), the genetic mechanism of Total Anomalous Pulmonary Venous Return (TAPVR) remains unknown, although previous studies have revealed potential disease-driving regions/genes. Blood samples collected from the 6 sporadic TAPVR cases and 81 non-TAPVR controls were subjected to whole exome sequencing. All detected variations were confirmed by direct Sanger sequencing. Here, we identified 2 non-synonymous missense mutations: c.C652T, p.R218W in activin A receptor type II-like 1 (ACVRL1), c.C717G, p.D239E in sarcoglycan delta (SGCD). Our results offered the landscape of mutations for TAPVR in Chinese population firstly and are valuable in the mutation-based pre- and post-natal screening and genetic diagnosis for TAPVR.

Causes of interruptions in postoperative enteral nutrition in children with congenital heart disease.

BACKGROUND AND OBJECTIVES: Perioperative nutritional support has become a hot topic in the clinical management of congenital heart disease (CHD). Postoperative enteral nutrition (EN) offers many benefits, such as protection of the intestinal mucosa, reduced risk of infection, and low clinical costs. Interruptions in EN frequently influence nutritional support and clinical outcomes. We, therefore, aimed to determine the causes of interruptions in postoperative EN in CHD patients and discuss clinical counter measures. METHODS AND STUDY DESIGN: We analyzed the data of 360 CHD patients to determine the causes of interruptions in postoperative EN and develop possible clinical strategies to prevent such interruptions. RESULTS: Of the 360 patients (aged from 1 month to 6 years), 198 patients had at least one EN interruption. The total number of interruptions was 498 (average, 2.52 interruptions/ patient). Non-gastrointestinal factors (airway management, fluid overload, invasive procedure, increased intracranial pressure, feeding tube block, and clinical deterioration) accounted for 67.8% (338/498) of all interruptions and gastrointestinal factors (vomiting, gastrointestinal bleeding, diarrhea, constipation, and large gastric residual volume) accounted for 32.2% (160/498). The total number of interruptions and the number of interruptions due to gastrointestinal factors were significantly higher in younger patients (aged from 1-12 months) than in older patients (aged from 1-6 years). CONCLUSIONS: Non-gastrointestinal factors were the main causes of interruptions in postoperative EN in CHD patients. Younger patients had a greater number of interruptions as a whole, and more interruptions caused by gastrointestinal factors. Gastrointestinal factors can be reduced by tube feeding and use of gastrointestinal motility drugs.

Percutaneous Punctured Transcatheter Device Closure of Residual Shunt after Ventricular Septal Defect Repair.

Ventricular septal defects (VSDs) are estimated to account for 20 to 30% of all congenital heart defects (CHDs). Although a residual shunt is the most common complication of VSD surgery, a second operation that applies the surgical repair method is very difficult because it can increase the possibility of uncontrolled bleeding and the severity of tissue adhesion. Here, we present the first case of percutaneous punctured transcatheter device closure of a residual shunt after VSD repair as a novel method to further develop for the treatment of children with congenital heart disease.

Risk-Benefit Profile of Gastric vs Transpyloric Feeding in Mechanically Ventilated Patients: A Meta-Analysis.

BACKGROUND: The risk-benefit profile of transpyloric vs gastric feeding in mechanically ventilated (MV) patients has not been definitively established. OBJECTIVE: To evaluate the risks and benefits of transpyloric feeding compared with gastric feeding in mechanically ventilated patients. DESIGN: We systematically searched MEDLINE, Google Scholar, EMBASE, and the Cochrane Central Register of Controlled Trials databases for eligible articles through June 21, 2013. Randomized controlled trials (RCTs) that reported a comparison between gastric and transpyloric feeding in MV patients were selected. Two reviewers independently extracted data on populations, methods, outcomes, and risk of bias. Ventilator-associated pneumonia (VAP) was considered the primary outcome. RESULTS: A total of 8 RCTs, including 835 MV patients, were identified and analyzed. Our pooled findings indicated that there was a significant reduction in VAP through transpyloric feeding compared with gastric feeding (relative risk [RR], 0.67; 95% confidence interval [CI], 0.53 to 0.85; P = .001) but not in mortality (RR, 1.08; 95% CI, 0.86 to 1.36; P = .49), length of mechanical ventilation (mean difference [MD], -0.16; 95% CI, -0.75 to 0.43; P = .59), length of stay in the intensive care unit (MD, -0.91; 95% CI, -2.75 to 0.94; P = .34), incidence of diarrhea (RR, 0.9; 95% CI, 0.66 to 1.23; P = .50), and incidence of vomiting (RR, 0.82; 95% CI, 0.25 to 2.72; P = .75). CONCLUSIONS: Transpyloric feeding in MV adults was associated with significantly less incidence of VAP compared with gastric feeding. No differences were observed in other outcomes, suggesting that the difference observed in the incidence of VAP may be spurious and needs confirmation.

Hybrid procedure with cardiopulmonary bypass for muscular ventricular septal defects in children.

OBJECTIVE: To summarize the technique and clinical experience of the hybrid procedure with cardiopulmonary bypass in children with muscular ventricular septal defect (mVSD). METHODS: From January 2006 to June 2010, 45 cases of mVSD underwent hybrid procedures with cardiopulmonary bypass (CPB) under the guidance of transesophageal echocardiography. mVSDs were closed with devices under direct vision in the 45 cases. Fourteen patients had another lesion that required surgical repair. Large membranous VSDs were closed with a pericardial patch after the initiation of CPB in 38 cases. RESULTS: Out of the 45 cases, 42 had only one occluder and three had two occluders. The size of the device for mVSD closure ranged from 3 to 8mm. All cases recovered smoothly after treatment without residual shunting, aortic or mitral valve regurgitation, or restriction of surrounding structures. All the children survived the operation with no late deaths during the follow-up. CONCLUSION: The hybrid procedure is safe and effective for the closure of congenital heart defects in children.

[The individualized surgical treatment of transposition of the great arteries].

OBJECTIVE: To discuss the effectiveness of individualized strategy of surgical management on the great arteries (TGA). METHODS: From March 1998 to October 2009, 127 cases (97 males and 30 females) with TGA were treated. There were 97 male and 30 female, aged from 4 hours old to 17 years old with a mean of (25 ± 37) months, weighted from 2.7 to 47.5 kg with a mean of (8 ± 8) kg. The palliative operations included Glenn operation in 14 cases (3 cases double Glenn procedure), Balalock-Taussing shunt in 14 cases, Banding operation in 8 cases, and atrial septal defect enlarge/Banding/Balalock-Taussing shunt in 15 cases. The end-stage operation included Senning procedure in 5 cases, Switch procedure in 32 cases, 2(nd)-stage Switch procedure in 11 cases, Switch procedure with VSD repairing in 20 cases, Switch procedure with Hybrid in 1 case, Nikaidoh procedure in 3 cases, Rastelli procedure in 13 cases, Fonton procedure in 18 cases, other procedure in 4 cases. Twenty-one cases underwent 2 operations, and 5 cases underwent 3 or more operations. Sixty-six cases underwent delayed sternal closure. RESULTS: There were 12 cases of death operatively in 127 cases. The total operative mortality was 9.4%. There were 5 cases dying of low cardiac output during the operation, 2 of pulmonary hypertension crisis, 2 of hemorrhage, 1 of grafting problem of coronary artery deformation, 1 of renal failure after Fonton procedure and 1 case of newborn dying of spontaneous rupture of liver post-operatively. The patients were followed up for 1 month to 12 years. There were 10 patients with vary degrees complications such as pulmonary stenosis, residual shunt and narrow channel. Three cases underwent reoperation. The rest of survived cases had normal heart function, good growth and development state. CONCLUSIONS: Individualized strategy of surgical management based on anatomical conditions of TGA can significantly improve the success rate of surgery and long-term survival.

[Effect of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats].

OBJECTIVE: To determine the effects of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats. METHODS: Fifty-four 3-week-old Sprague-Dawley rats were randomly and equitably divided into sham-operated group, model group and diazoxide group respectively (n = 18). The model of hypothermia cerebral ischemia reperfusion injury was made. After 24 hours of operation, the brains of rats were removed and preserved. The content of superoxide dismutase (SOD) and malonaldehyde (MDA) in brain tissue were detected. Cytosolic C release of cytochrome was confirmed by Western Blot. The protein expression of Caspase-3 was determined by immunohistochemistry. RESULTS: In the model group, the content of SOD was (198 +/- 41) U/mg, lower than the sham-operated group's (321 +/- 36) U/mg (P < 0.01). The content of MDA was (212 +/- 21) nmol/mg, was higher than the sham-operated group's (100 +/- 23) nmol/mg (P < 0.01), and the expressions of cytochrome C (0.72 +/- 0.09) and Caspase-3 (83 +/- 10) were all significantly higher than those in the sham-operated group (0.17 +/- 0.02 and 115 +/- 9) (P < 0.01). Compared with the model group, the content of SOD in the diazoxide group [(264 +/- 34) U/mg] was markedly increased (P < 0.05). In addition, diazoxide provided significant reductions in the content of MDA [(174 +/- 19) nmol/mg] and the expressions of cytochrome C (0.41 +/- 0.05) and Caspase-3 (99 +/- 11) (P < 0.05). CONCLUSIONS: The neuroprotective effects of diazoxide against brain injury induced by deep hypothermia cerebral ischemia reperfusion through inhibiting oxygen free radicals and cell apoptosis. Diazoxide may become a new neuroprotective drug after infant complicated congenital cardiac operation.

Neuroprotective effect of diazoxide on brain injury induced by cerebral ischemia/reperfusion during deep hypothermia.

OBJECT: The purpose of this study was to determine the effects of diazoxide on apoptosis and the relative mechanisms in a model of brain injury induced by cerebral ischemia/reperfusion (I/R) during deep hypothermia. METHODS: Three-week-old Sprague-Dawley male rats were randomly and equitably divided into sham-operated group, placebo-treated group and diazoxide-treated group respectively. Specific examination of the regional cerebral blood flow (rCBF) was measured in the three groups continuously during the operation by laser Doppler flowmetry. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was showed DNA fragmentation. The mRNA expressions of cytochrome c and full-length caspase-3 were determined by RT-PCR, while the protein expressions of cytochrome c and cleaved caspase-3 were determined by immunohistochemistry at 1 h, 6 h, 24 h, 72 h and 7 days after I/R, respectively. Cytosolic release of cytochrome c at 24 h after I/R was also confirmed by Western blot. RESULTS: rCBF was significantly decreased in both of placebo-treated and diazoxide-treated group just after ischemia in the time interval 0-5 min, and had no obvious changes in all the time intervals during the operation. Diazoxide preconditioning significantly decreased the percentage of TUNEL-positive staining cells. The mRNA expressions of cytochrome c and full-length caspase-3 in diazoxide-treated group were significantly decreased. In addition, diazoxide provided a significant reduction in the protein expressions of cytochrome c and cleaved caspase-3. CONCLUSION: These results suggested that the neuroprotective effects of diazoxide against cerebral I/R injury during deep hypothermia correlated with the reduction of DNA fragmentation, prevention of mitochondrial cytochrome c release and inhibition of caspase-3 activation.