Cell Nucleus ; Cellular Senescence/genetics* ; CRISPR-Cas Systems/genetics*

Objective:To investigate the morphological characteristics and operative methods of mixed total anomalous pulmonary venous connection (TAPVC), and to analyze the risk factors of postoperative death.Methods:From January 2011 to January 2019, 17 cases of mixed TAPVC were operated in Department of Cardiovascular Surgery, Beijing Children′s Hospital, Capital Medical University, with 10 males and 7 females.The average age was (4.4±3.8) months (1-15 months) and the average body mass was (5.6±1.7) kg (3.5-10.0 kg), including 1 case of ventricular septal defect, 17 cases of atrial septal defect and 15 cases of ductus arteriosus.Preoperative pulmonary vein stenosis was discovered in 4 cases and severe pulmonary hypertension was in 10 cases.A total of 5 cases needed ventilator support before operation, and 2 cases needed emergency operation.The diagnosis was confirmed by color Doppler ultrasound and CT before operation.There were 2 cases of type Ⅰ (type 2+ 2), 13 cases of type Ⅱ (type 3+ 1), and 2 cases of type Ⅲ (anatomic variant).Results:All the patients were treated through operation.The principle of operation was to correct all pulmonary veins to the left atrium.The cardiopulmonary bypass time was (182.3±122.8) min, the aortic occlusion time was (84.3±15.9) min, the postoperative ventilator support time was (92.9±70.0) h, and the monitoring room time was (6.9±4.9) d. In this group, 3 cases died in hospital (17.6%) and 1 case died out of hospital (5.9%).Conclusions:The mortality of mixed TAPVC type Ⅲ was high, while preoperative pulmonary vein stenosis, severe pulmonary hypertension and the combination of sub-cardiac type were the important risk factors of death.The operation mode depends on the anatomic drainage mode, so individualized operation is recommended.

Objective:To investigate the diagnosis, surgical methods, perioperative treatment and surgical results of Kommerell's diverticulum with double aortic arch in infants.Methods:From December 2014 to December 2019, 22 cases of double aortic arch combined with Kommerell diverticulum were operated in our hospital, 14 males and 8 females, with an average age of (13.7±11.6) months (1-36 months) and mean body mass of (9.8±3.4)kg (5-20 kg). The children had respiratory symptoms such as asthmatic suffocation, shortness of breath, repeated respiratory tract infection and chronic cough before operation. All patients underwent cardiac CT examination. The average diverticulum was 8 mm×9 mm, in the trachea The average compression degree of the lower segment was 56%±16% (30%-80%). The distal part of the left arch was atresia and Kommerell's diverticulum was found in all patients. The operation methods were left aortic arch separation, ligament separation and diverticulectomy. In one case, tracheal stent was placed simultaneously during the operation because of severe tracheal malacia.Results:The average time in the ward was(1.4±0.8)days (1-4)days, and the average time in hospital was (6.7±2.8)days (4-13 days). The average follow-up period was (25.5±16.9) months (2-60 months). During the follow-up period, 18 children had no persistent respiratory symptoms, and 4 children had only slight respiratory symptoms.Conclusion:Kommerell's diverticulum can also be combined with double aortic arch. The operation method is to separate the aortic arch and ligament at the atresia end and resect the diverticulum at the same time. It has a good early prognosis and may eliminate the residual symptoms and late complications.

Objective To investigate the diagnosis, surgical treatment and surgical results of infantile left subclavian ar-tery combined with Kommerell diverticulum.Methods In our hospital from 2014 to 2017, there were 15 cases of left subclavi-an artery combined with Kommerell diverticulum, 10 males and 5 females, average age 11.8 months(2 to 48 months), average weight of 9.2kg(4 -24 kg), including 3 cases with ventricular septal defect ( VSD), and 1 cases of coarctation of aorta (COA).Children with postoperative respiratory difficulty, recurrent respiratory infection, chronic cough and other respiratory symptoms, preoperative detection of airway and or esophagus compression performance after cardiac computed tomography ex-amination confirmed, general anesthesia, thoracotomy or left chest lateral thoracotomy, cut off arterial ligaments and Kommerell diverticulum Resection and vagal left subclavian artery transplantation were performed in the left common carotid artery com-bined with cardiac malformation.Results All the children were cured and discharged from hospital.The follow-up and mid-term recovery were good.Conclusion Infants with airway and esophageal compression may have aberrant left subclavian artery combined with Kommerell diverticulum , cardiac CT is an effective means to diagnose this disease .Removal of the associated Kommerell diverticulum and transferring the left subclavian artery to the left common carotid artery , as the main operative meth-od has good early prognosis,and may eliminate residual symptoms and late complications .

To screen the pathogenic mutation location in a genetic family with the neurofibromatosis (NF1) by the next generation sequencing and analyze the clinical phenotype,Illumina Miseq sequencing was applied to capture and analyze the target regions of NF1 family's probands,and furtherly find out the suspicious mutations,as well as to verify the family members by Sanger sequencing.Two rare variants were identified in proband,including the heterozygous missense mutation c.C3649T (p.P1217S) in KIF1B gene and the missense mutation c.T6311C (p.L2104P) on exon 41 of NF1 gene (NM_000267.3).The amino acid at position 2104 was found to be changed from leucine to proline in NF1.The protein prediction SIFT and Polyphen-2 values were 0,0.997,which predicted a conformational change in the encoded protein and eventually affected its function.The mutation c.T6311C in NF1 gene was detected in all patients in this family,which showed genetic co-segregation.The clinical phenotype was neurofibroma in the spinal canal.There were no café au lait spots,iris Lisch nodules,scoliosis,tinnitus,heating loss,or elevated intracranial pressure.The missense mutation c.T6311C (p.L2104P) in NF1 gene might be the genetic cause of this hereditary disease of neurofibromatosis.

Objective To observe the inhibitory effect of matrine on K-ras gene mutation colon cancer, and to clarify the inhibitory mechanism. Methods SW480 cells were treated with different concentrations of matrine. MTS method was used to detect the proliferation of SW480 cell lines. The apoptosis of SW480 cells was measured by flow cytometry. The migration of SW480 cells was examined by the scratch test. The expression of MEK1/2 protein was detected by Western blotting method. Results Compared with the blank control group, matrine (0.125-1 mg/mL) could inhibit the growth and proliferation of human colorectal cancer SW480 cell lines, promote the apoptosis, restrain the migration of SW480 cells, and inhibit the expression of MEK1/2 protein(P < 0.05), the effect showing a dose-dependent trend. Conclusion Matrine can effectively inhibit the proliferation and migration of SW480 cells, and promote SW480 cell apoptosis through the down-regulation of MEK1/2 protein expression in MAPK signal pathway system.

Purpose Using quantitative morphometric techniques, To analyzse the developmental characteristics of pulmonary arterial and alveolar with a porcine model of cyanotic congenital heart defect with decreased pulmonary blood flow that we had established. Methods Lung biopsy specimens were taken from animals of control ( C) and cyanosis ( D) groups and than sectioned and stained. The morphological observation and the method of half-quantitative morphometric technique were applied to measure the following char-acteristics:the media thickness ( MT) and the percentage of media thickness ( MT%) , the media section area ( MS%) and the per-centage of media section area ( MS) , the numbers of micro-arteries per square centimeter ( APSC) . In addition, we calculated the ratio of CMA, PMA and NMA in the same section of lung biopsy specimens. Results There showed universally distended, irregular and thin-walled vessels in the lung biopsy specimens of group D under the light microscope. There was an increased number of pulmonary arteries whose media were hypoplastic. The MT, MT% and MS, MS% in group D were significantly less than those of group C ( all P<0. 001), the APSC was also less in group D than in group C (P<0. 01), but MAN were not significantly different between two groups (P>0. 05). Electron microscopy revealed endothelial swell and irregularity, a thinned basement membrane, a disorganized or disrupted elastic fibers layer. The smooth muscle of vascular media shrunk. In addition to these, other changes included the mitochon-drion vacuolization, a diminished cellular organelle and type Ⅱ alveolar epithelial hyperplasia. Conclusion The pulmonary vessels are evidently hypoplastic or degenerated in cyanotic congenital heart defect with decreased pulmonary blood flow, and the function is thought to be influenced by the morphological changes. To promote the pulmonary artery growth and improve this pathophysiological state, it is critical to increase the pulmonary blood flow.

BACKGROUNDCardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming.

METHODSTwenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n = 10) and control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. The volume of the priming solution, composed of 6% HES 130/0.4 and 125 IU heparin, was less than 12 ml. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rat of 100-120 ml × kg (-1)× min(-1) in CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg.

RESULTSAll CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable.

CONCLUSIONSThe establishment of CPB without blood priming in rats can be achieved successfully. The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

Animals ; Cardiopulmonary Bypass ; methods ; Lung Injury ; surgery ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDLarge animal cardiopulmonary bypass (CPB) models are expensive, and prevent assessment of neurocognitive function, and difficulties with long-term recovery. The purpose of this study was to establish a novel rat model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.

METHODSTwenty adult male Sprague-Dawley rats weighing 450-560 g were randomized to CPB with deep hypothermic circulatory arrest (DHCA) and control groups, with 10 rats each. The experimental protocols, including blood and crystalloid fluid administration, anesthesia, orotracheal intubation, ventilation, cannulation, and heparinization were identical in both groups. After inducing cardiac arrest, the circuit was turned off and rats were left in a DHCA state for 15 minutes. Rats were rewarmed to 34°C to 35°C over a period of 36 to 42 minutes using CPB-assisted rewarming, a heating blanket, and a heating lamp along with administration of 0.1 mEq of sodium bicarbonate and 0.14 mEq of calcium chloride. The remaining priming volume was reinfused and animals were weaned from CPB.

RESULTSAll CPB with DHCA processes were successfully achieved. Blood gas analysis and hemodynamic parameters were in the normal range. The vital signs of all rats were stable.

CONCLUSIONSOur CPB circuit has several novel features, including a small priming volume, active cooling/rewarming processes, vacuum-assisted venous drainage, peripheral cannulation without thoracotomy or sternotomy, and an accurate means of monitoring peripheral tissue oxygenation.

Animals ; Cardiopulmonary Bypass ; methods ; Circulatory Arrest, Deep Hypothermia Induced ; methods ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar