Publications by authors named "Zhuoming Xu"

24 Publications

  • Page 1 of 1

MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis.

Mol Cell Biochem 2021 Aug 2. Epub 2021 Aug 2.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, No.1678 Dongfang Road, Pudong New Area, Shanghai, 200127, China.

The present study aimed to evaluate the potential roles of MIR3142HG, a novel long non-coding RNA (lncRNA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was simulated by the treatment of LPS in human pulmonary microvascular endothelial cells (HPMECs). The expression of MIR3142HG, miR-450b-5p and high-mobility group box 1 (HMGB1) was determined by real-time PCR and western blotting. Functional analysis was performed through the assessment of cell viability, apoptosis and the production of proinflammatory cytokines. The interactions among MIR3142HG, miR-450b-5p and HMGB1 were analyzed by bioinformatics methods, dual-luciferase reporter and RNA pull-down assays. Using gain- and loss-of-function approaches, the in vitro functions of MIR3142HG and miR-450b-5p were subsequently assessed. MIR3142HG expression was upregulated, while miR-450b-5p was decreased in LPS-treated HPMECs. MIR3142HG knockdown protected against ALI induced by LPS through alleviating the apoptosis and inflammation of HPMECs. MIR3142HG impaired miR-450b-5p-mediated inhibition of HMGB1. Besides, the effects of MIR3142HG silencing could be alleviated by miR-4262 inhibition or HMGB1 overexpression. MIR3142HG mediated LPS-induced injury of HPMECs by targeting miR-450b-5p/HMGB1, suggesting that MIR3142HG might serve as a therapeutic potential for the treatment of ALI.
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http://dx.doi.org/10.1007/s11010-021-04209-yDOI Listing
August 2021

Postcardiotomy Extracorporeal Membrane Oxygenation in Neonates.

Thorac Cardiovasc Surg 2021 12 29;69(S 03):e41-e47. Epub 2021 Jul 29.

Department of Pediatric Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Extracorporeal membrane oxygenation (ECMO) provides circulatory support in children with congenital heart disease, particularly in the setting of cardiopulmonary failure and inability to wean from cardiopulmonary bypass. This study summarized the clinical application of ECMO in the treatment of heart failure after cardiac surgery in neonates.

Materials And Methods: Clinical data of 23 neonates who received ECMO support in our center from January 2017 to June 2019 were retrospectively analyzed.

Results: Twenty-three neonates, aged from 0 to 25 days and weight between 2,300 and 4,500 g, with heart failure postcardiotomy were supported with ECMO. The successful weaning rate was 78.26% and discharge rate was 52.17%. Bleeding and residual malformation were the most common complications. The univariate analysis showed that nonsurvivors were related to the factors such as higher lactate value of ECMO 12 and 24 hours ( = 0.008 and 0.001, respectively), longer time to lactate normalization ( = 0.001), lactate > 10 mmol/L before ECMO ( = 0.01), lower weight ( = 0.01), longer ECMO duration ( = 0.005), lower platelet count ( = 0.001), more surgical site bleeding ( = 0.001), and surgical residual malformation ( = 0.04). Further logistic regression analysis revealed that higher lactate value of ECMO 24 hours ( = 0.003), longer ECMO duration ( = 0.015), and surgical site bleeding ( = 0.025) were independent risk factors.

Conclusion: ECMO was an effective technology to support the neonates with cardiopulmonary failure after open heart surgery. Control the lactate acidosis and surgical site bleeding event may be helpful for patients' recovery.
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http://dx.doi.org/10.1055/s-0041-1730034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324001PMC
December 2021

Elevated Arterial-Central Venous Carbon Dioxide Partial Pressure Difference Indicates Poor Prognosis in the Early Postoperative Period of Open Heart Surgery in Infants with Congenital Heart Disease.

Pediatr Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Cardiac Intensive Care Unit, Department of Cardiovascular and Thoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.

Background: Elevated arterial-central venous carbon dioxide partial pressure difference (AVCO) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes.

Methods: Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3 h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42 h after surgery. Clinical data of all patients were recorded.

Results: A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO/VO] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO/VO > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO to predict DO/VO ≤ 2 was 12.3 within 42 h of surgery with area under the curve of 0.84. High AVCO is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit.

Conclusion: Elevated AVCO within 42 h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO indicates poor prognosis.
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http://dx.doi.org/10.1007/s00246-021-02646-6DOI Listing
June 2021

Is a Hub lncRNA ceRNA in Hearts With Tetralogy of Fallot Which Regulates Congenital Heart Disease Genes Transcriptionally and Epigenetically.

Front Cell Dev Biol 2021 11;9:630634. Epub 2021 May 11.

Cardiac Intensive Care Unit, Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Heart development requires robust gene regulation, and the related disruption could lead to congenital heart disease (CHD). To gain insights into the regulation of gene expression in CHD, we obtained the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in 22 heart tissue samples with tetralogy of Fallot (TOF) through strand-specific transcriptomic analysis. Using a causal inference framework based on the expression correlations and validated microRNA (miRNA)-lncRNA-mRNA evidences, we constructed the competing endogenous RNA (ceRNA)-mediated network driven by lncRNAs. Four lncRNAs (, , , and ) were identified as hub lncRNAs in the network. was selected for further study since all its targets were CHD-related genes (, , and ). Both and could bind with hsa-miR-421, which has been validated using dual-luciferase reporter assays. Knockdown of not only significantly reduced and expression in HEK 293 and the fetal heart cell line (CCC-HEH-2) but also increased the transcription of its interacted miRNAs in a cell-specific way. Besides ceRNA mechanism, RNAseq and ATACseq results showed that might play repression roles in heart development by transcriptionally regulating CHD-related genes. In conclusion, we identified a ceRNA network driven by lncRNAs in heart tissues of TOF patients. Furthermore, we proved that , one hub lncRNA in the TOF heart ceRNA network, regulates multiple genes transcriptionally and epigenetically.
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http://dx.doi.org/10.3389/fcell.2021.630634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144506PMC
May 2021

Long Noncoding RNA Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB.

Front Cell Dev Biol 2021 10;9:660576. Epub 2021 May 10.

Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Congenital heart defects (CHDs) are the most common birth defects worldwide. 22q11.2 deletion syndrome is the most common microdeletion disorder that has been frequently associated with conotruncal malformations. By now, the dosage-sensitive gene has been adopted as the major pathogenic gene responsible for 22q11.2 deletion, which is regulated by canonical Wnt/β-catenin signaling pathway in heart outflow tract development. Here, we report the long noncoding RNA (lncRNA) , which is encompassed in the 22q11.2 region, that can activate canonical Wnt/β-catenin signaling by protecting β-catenin from degradation, which could result from decreased ubiquitination. Such effects were mediated by two short heat shock proteins HSPA6 and α-β-crystallin (CRYAB), whose expression was regulated by through a competing endogenous RNA (ceRNA) mechanism. In clinical practice, the pathogenesis of copy number variation (CNV) was always attributed to haploinsufficiency of protein-coding genes. Here, we report that the 22q11.2 lncRNA significantly activated canonical Wnt/β-catenin signaling, which has major roles in cardiac outflow tract development and should act upstream of . Our results suggested that lncRNAs should contribute to the etiology of CNV-related CHD.
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http://dx.doi.org/10.3389/fcell.2021.660576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141806PMC
May 2021

Effects of repairing ventricular septal defects with right vertical infra-axillary mini-incision on lung function and postoperative analgosedation.

Exp Ther Med 2021 Apr 29;21(4):302. Epub 2021 Jan 29.

Department of Cardiac Intensive Care Unit, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.

The present study aimed to assess the effects of repairing ventricular septal defects (VSDs) with right vertical infra-axillary mini-incision (RVAI). A total of 116 patients with VSDs were prospectively enrolled and underwent cardiac surgery between June 2017 and December 2018 at the cardiac intensive care unit of Shanghai Children's Medical Center (Shanghai, China). Of these, 58 patients underwent the RVAI procedure and 58 patients matched 1:1 underwent the standard median sternotomy incision (MSI) procedure and were designated as the control group. The demographic data and clinical outcomes intra- and postoperatively were compared. A bedside lung ultrasound was performed to evaluate the degree of lung injury and the number of B-lines was quantified and compared between the two groups. The sedation and analgesia levels were also assessed after the operation. No significant difference was identified between the two groups regarding the overall cardiopulmonary bypass or aortic cross-clamp time. All patients were extubated within 8 h. The RVAI group had shorter incision lengths (median, 4.6 cm) and less drainage (median, 15 ml) than the MSI group. Furthermore, compared to the MSI group, the RVAI group had a significantly higher number of B-lines in the right lung regions immediately after surgery and at 12 h postsurgery (24.1 and 5.2%, respectively) but eventually exhibited no differences at 24 and 36 h postsurgery; by contrast, there were no differences in the left lung regions. The bedside bispectral index score and the Face, Legs, Activity, Cry, Consolability scale score exhibited no significant differences after the operation. In conclusion, the RVAI procedure appears to be a safe alternative for repairing VSDs in addition to satisfactory cosmetic results and the incision does not interfere with postoperative analgosedation.
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http://dx.doi.org/10.3892/etm.2021.9733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885067PMC
April 2021

Medical Image-Based Hemodynamic Analyses in a Study of the Pulmonary Artery in Children With Pulmonary Hypertension Related to Congenital Heart Disease.

Front Pediatr 2020 2;8:521936. Epub 2020 Dec 2.

Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pulmonary hypertension related to congenital heart disease (PH-CHD) is a devastating disease caused by hemodynamic disorders. Previous hemodynamic research in PH-CHD mainly focused on wall shear stress (WSS). However, energy loss (EL) is a vital parameter in evaluation of hemodynamic status. We investigated if EL of the pulmonary artery (PA) is a potential biomechanical marker for comprehensive assessment of PH-CHD. Ten PH-CHD patients and 10 age-matched controls were enrolled. Subject-specific 3-D PA models were reconstructed based on computed tomography. Transient flow, WSS, and EL in the PA were calculated using non-invasive computational fluid dynamics. The relationship between body surface area (BSA)-normalized EL ( ) and PA morphology and PA flow were analyzed. Morphologic analysis indicated that the BSA-normalized main PA (MPA) diameter (D), MPA/aorta diameter ratio (D/D), and MPA/(left PA + right PA) [D/D] diameter ratio were significantly larger in PH-CHD patients. Hemodynamic results showed that the velocity of the PA branches was higher in PH-CHD patients, in whom PA flow rate usually increased. WSS in the MPA was lower and was higher in PH-CHD patients. was positively correlated with D, D/D, and D/D ratios and the flow rate in the PA. was a sensitive index for the diagnosis of PH-CHD. is a potential biomechanical marker for PH-CHD assessment. This hemodynamic parameter may lead to new directions for revealing the potential pathophysiologic mechanism of PH-CHD.
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http://dx.doi.org/10.3389/fped.2020.521936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738347PMC
December 2020

Induction of NEDD8-conjugating enzyme E2 UBE2F by platinum protects lung cancer cells from apoptosis and confers to platinum-insensitivity.

Cell Death Dis 2020 11 12;11(11):975. Epub 2020 Nov 12.

Cancer Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, China.

Platinum is a widely used first-line chemotherapy in treating non-small cell lung cancer of adenocarcinoma. Unfortunately, platinum resistance leads to relapse and therapeutic failure, enabling the development of platinum-sensitization strategies to be of great clinical significance. Here, we report that the upregulation of the NEDD8-conjugating enzyme UBE2F is an important way for lung cancer cells to escape platinum-induced cell apoptosis, which confers to insensitivity to platinum-based chemotherapy. Mechanistically, platinum treatment impairs the complex formation for proteasome-mediated UBE2F degradation, evidenced by the weaker association between UBE2F and Ring-box protein 1 (RBX1), an essential component of Cullin-Ring E3 ligases (CRLs), thus leading to the accumulation of UBE2F. The accumulated UBE2F promotes the neddylation levels and activity of Cullin5, in accord with the lower expression of pro-apoptotic protein NOXA, a well-known substrate of Cullin-Ring E3 ligase 5 (CRL5). Additionally, knockout of UBE2F significantly sensitizes lung cancer cells to platinum treatment by enhancing the protein levels of NOXA and subsequently promoting cell apoptosis. Our observations uncover a previously unknown regulatory mechanism of UBE2F stability upon platinum chemotherapy and suggest that UBE2F might be a novel therapy target for sensitizing lung cancer cells to platinum-based chemotherapy.
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http://dx.doi.org/10.1038/s41419-020-03184-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665193PMC
November 2020

Pressure Overload Greatly Promotes Neonatal Right Ventricular Cardiomyocyte Proliferation: A New Model for the Study of Heart Regeneration.

J Am Heart Assoc 2020 06 30;9(11):e015574. Epub 2020 May 30.

Institute of Pediatric Translational Medicine Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine Shanghai China.

Background Current mammalian models for heart regeneration research are limited to neonatal apex amputation and myocardial infarction, both of which are controversial. RNAseq has demonstrated a very limited set of differentially expressed genes between sham and operated hearts in myocardial infarction models. Here, we investigated in rats whether pressure overload in the right ventricle, a common phenomenon in children with congenital heart disease, could be used as a better animal model for heart regeneration studies when considering cardiomyocyte proliferation as the most important index. Methods and Results In the rat model, pressure overload was induced by pulmonary artery banding on postnatal day 1 and confirmed by echocardiography and hemodynamic measurements at postnatal day 7. RNA sequencing analyses of purified right ventricular cardiomyocytes at postnatal day 7 from pulmonary artery banding and sham-operated rats revealed that there were 5469 differentially expressed genes between these 2 groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes mainly mediated mitosis and cell division. Cell proliferation assays indicated a continuous overproliferation of cardiomyocytes in the right ventricle after pulmonary artery banding, in particular for the first 3 postnatal days. We also validated the model using samples from overloaded right ventricles of human patients. There was an approximately 2-fold increase of Ki67/pHH3/aurora B-positive cardiomyocytes in human-overloaded right ventricles compared with nonoverloaded right ventricles. Other features of this animal model included cardiomyocyte hypotrophy with no fibrosis. Conclusions Pressure overload profoundly promotes cardiomyocyte proliferation in the neonatal stage in both rats and human beings. This activates a regeneration-specific gene program and may offer an alternative animal model for heart regeneration research.
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http://dx.doi.org/10.1161/JAHA.119.015574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429015PMC
June 2020

Risk factors of malnutrition in Chinese children with congenital heart defect.

BMC Pediatr 2020 05 13;20(1):213. Epub 2020 May 13.

Cardiac Intensive Care Unit, Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China.

Background: The study aimed to investigate the risk factors of malnutrition in children with congenital heart defect (CHD) in China.

Methods: This cohort study was performed at the biggest pediatric heart center in China; 3252 patients with CHD who underwent cardiac surgeries in 2013 were included. Anthropometric measurements included weight for age Z score (WAZ), weight for height Z score (WHZ), and height for age Z score (HAZ). The patients were classified as normal nutritional status and malnutrition, based on a cut-off Z score of <- 2. Factors associated with malnutrition were determined using logistic regression analysis.

Results: The prevalence of preoperative WAZ < -2 (underweight), HAZ < -2 (stunting), and WHZ < -2 (wasting) was 23.3, 23.3, and 14.3%, respectively. The multivariable analysis of preoperative malnutrition showed that hospitalization, age at surgery, risk adjustment for congenital heart surgery-1 > 3, mechanical ventilation, pulmonary hypertension, and acyanotic heart disease were associated with underweight. Parents' height, single ventricle, and cyanotic heart disease were associated with stunting. Hospitalization and pulmonary hypertension were associated with wasting. After surgery, the patients presented a significant improvement in growth within the first year in all three parameters and grew to the normal range of WAZ (- 0.3 ± 0.9, P < 0.001), HAZ (0.2 ± 0.8, P = 0.001), and WHZ (0.03 ± 0.6, P < 0.001) at 2 years after surgery. The prevalence of underweight, stunted, and wasting declined to 3.2, 2.7, and 1.9% 3 years after surgery. Malnutrition after surgery was associated with cardiac residual cardiac abnormalities (OR = 35.3, p < 0.0001), high Ross classification of heart function (OR = 27.1, p < 0.0001), and long-term taking oral diuretics (OR = 20.5, P = 0.001).

Conclusions: Malnutrition is still a problem in children with CHD in China, especially before the surgery. There is need to strengthen the nutrition support for children with CHD before surgery. Hemodynamic factors were found to be the risk factors associated with malnutrition after operation.
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http://dx.doi.org/10.1186/s12887-020-02124-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218652PMC
May 2020

Computational Evaluation of Surgical Design for Multisegmental Complex Congenital Tracheal Stenosis.

Biomed Res Int 2020 20;2020:3509814. Epub 2020 Apr 20.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Multisegmental complex congenital tracheal stenosis (CTS) is an uncommon but potentially life-threatening malformation of the airway. Staged surgery is indicated for the complex pathophysiology of the abnormal trachea. Surgical intervention to fix the stenotic segments may result in different postoperative outcomes. However, only few studies reported the design of surgical correction for multisegmental CTS. We used computer-aided design (CAD) to simulate surgical correction under different schemes to develop a patient-specific tracheal model with two segmental stenoses. Computational fluid dynamics (CFD) was used to compare the outcomes of different designs. Aerodynamic parameters of the trachea were evaluated. An obvious interaction was found between the two segments of stenosis in different surgical designs. The surgical corrective order of stenotic segments greatly affected the aerodynamic parameters and turbulence flows downstream of tracheal stenosis and upstream of the bronchus. Patient-specific studies using CAD and CFD minimize the risk of staged surgical correction and facilitate quantitative evaluation of surgical design for multiple segments of complex CTS.
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http://dx.doi.org/10.1155/2020/3509814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191439PMC
February 2021

Effects of Different Modes of Mechanical Ventilation on Aerodynamics of the Patient-specific Airway: A Numerical Study

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:4961-4964

Mechanical ventilation (MV) is an effective management strategy for neonates with critical congenital heart disease or congenital tracheal stenosis (CTS). However, there is no standard for patient-specific mode selection. This study numerically investigated the aerodynamic effects of tracheal model with severe stenosis when by different levels of ventilator assist during Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA). Based on medical images, a three-dimensional (3D) tracheal model with insertion of a cuffed endotracheal tube was reconstructed. The technology of Computational Fluid Dynamics (CFD) was applied to simulate the airflow in the trachea. The aerodynamic parameters, including pressure drop (PD), streamlines and rate of energy loss (ELR), were compared to assess the MV effects. The results indicated that high assist level, accompanied by high airflow velocity, should be the main cause of aerodynamic disorders in the airway during MV. Lower PD, ELR and relatively steady velocity of NAVA was observed. Compare with PSV, it was inferred that preserved auto-regulation of respiration during NAVA may have potential advantages for flow rate regulation in patient with CTS. CFD analysis is a potential noninvasive tool for obtaining tracheal aerodynamics, which will be helpful for making decisions of appropriate MV mode.
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http://dx.doi.org/10.1109/EMBC.2019.8856357DOI Listing
July 2019

Characteristics of Pulmonary Vascular Remodeling in a Porcine Model of Shunt-Associated Pulmonary Arterial Hypertension.

Pediatr Cardiol 2020 Apr 3;41(4):669-676. Epub 2020 Jan 3.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China.

Lung biopsy is the gold standard for evaluating pathological changes in the pulmonary vascular bed. Knowing the distribution characteristics of pulmonary vascular lesions can improve the accuracy of lung biopsy. To investigate the distribution characteristics of pulmonary vascular remodeling, a reliable porcine model of shunt-associated pulmonary arterial hypertension (PAH) was established. Twenty piglets were randomly divided into the experimental group (n = 10) and the control group (n = 10). A modified Blalock-Taussig shunt (MBTS, left innominate artery to main pulmonary artery) was created surgically in the experimental group. Three months later, an invasive catheter was used to obtain hemodynamic parameters, and lung biopsy was performed to assess the remodeling of pulmonary vascular bed. MBTS was successfully implemented in six piglets. There's no significant difference in hemodynamic parameters of the two groups before the shunt. However, these parameters and right ventricular hypertrophy index of the experimental group were significantly increased after three months shunting. Pathological changes in the experimental group, including thickening of pulmonary artery media, intimal fibrosis, and right ventricular hypertrophy, were observed. Furthermore, the percentage of media thickness and medial area of the experimental group were significantly higher than control group. Histopathology showed that vascular remodeling of the lung was inhomogeneous and that the lateral lesion was more severe than other segments. These results indicated that MBTS could be used to establish a reliable porcine model of shunt-associated PAH and that multisite detection with different segments should be applied to assess the severity of pulmonary vascular remodeling.
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http://dx.doi.org/10.1007/s00246-019-02275-0DOI Listing
April 2020

Soluble triggering receptor expressed on myeloid cells-1 as a useful biomarker for diagnosing ventilator-associated pneumonia after congenital cardiac surgery in children.

Exp Ther Med 2019 Jan 31;17(1):147-152. Epub 2018 Oct 31.

Department of Infectious Disease, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.

The present study aimed to assess the usefulness of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in the diagnosis of ventilator-associated pneumonia (VAP) in paediatric patients with congenital heart disease (CHD) following cardiac surgery. The current prospective study enrolled 48 patients with congenital heart diseases who were suspected of having VAP; these patients were undergoing cardiac surgery between August 2016 and October 2017 in the Cardiac Intensive Care Unit of Shanghai Children's Medical Center (Shanghai, China). A total of 31 patients were diagnosed with VAP using a polymerase chain reaction (PCR) assay, while 17 patients without VAP were designated as the Non-VAP group. A bronchoscopy was performed and samples were collected for measurement on the day that VAP was diagnosed. The sTREM-1 levels were measured in bronchoalveolar lavage fluid (BALF) and exhaled ventilator condensate (EVC). BALF specimens were also sent to the microbiology laboratory for PCR assays and quantitative culturing. The positive detection rate of bacteria using the PCR assay and traditional culture was 64.6% (31/48) and 39.6% (19/48). sTREM-1 was significantly higher in the BALF (146.21 pg/ml vs. 118.06 pg/ml) and EVC (125.29 pg/ml vs. 120.48 pg/ml) of patients with VAP demonstrated compared with the patients without VAP. The findings suggest that the detection of sTREM-1 in BALF and EVC samples may be useful for the diagnosis of VAP following heart surgery in children.
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http://dx.doi.org/10.3892/etm.2018.6905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307413PMC
January 2019

Characteristics of Pulmonary Vascular Remodeling in a Novel Model of Shunt-Associated Pulmonary Arterial Hypertension.

Med Sci Monit 2018 Mar 19;24:1624-1632. Epub 2018 Mar 19.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong Universtiy School of Medicine, Shanghai, China (mainland).

BACKGROUND Establishing a shunt-induced pulmonary arterial hypertension (PAH) model in mice would be of great scientific value, but no such models have been reported to date. Here, we established a shunt-associated PAH in mice to investigate the characteristics of pulmonary vascular remodeling, which provides a new platform for the in-depth study of PAH associated with congenital heart disease (CHD). MATERIAL AND METHODS Eighty mice were randomly divided into the heavy shunt group (n=32), the small shunt group (n=32), the sham operation group (n=8), and the control group (n=8). The septum of the abdominal aorta and inferior vena cava was cut directly to create a heavy abdominal aortocaval shunt. Pulmonary artery pressure, right ventricular hypertrophy index, and lung tissue morphology were evaluated in the 4th, 6th, 8th, and 12th weeks in the shunt groups. RESULTS Shunt-associated PAH by abdominal aortocaval shunt in mice was successfully established. The shunt patency rate was significantly higher in the heavy shunt group. Significant differences were observed between the heavy shunt group and other groups in terms of pulmonary artery pressure and the right ventricular hypertrophy index. Tissue sections revealed a thickened pulmonary intimal layer and muscular layer and stenosis of the lumen in the shunt groups. Immunofluorescent assay results showed significant proliferations of PAH smooth muscle cells and endothelial cells, consistent with the clinical pulmonary vascular remodeling seen in human patients with severe PAH. CONCLUSIONS Shunt-associated PAH established by directly cutting the septum between the abdominal aorta and inferior vena cava is a stable and reliable model for research on PAH associated with CHD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870112PMC
http://dx.doi.org/10.12659/msm.905654DOI Listing
March 2018

Mechanical Ventilation After Bidirectional Superior Cavopulmonary Anastomosis for Single-Ventricle Physiology: A Comparison of Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist.

Pediatr Cardiol 2016 Aug 18;37(6):1064-71. Epub 2016 Apr 18.

Pediatric and Neonatal Intensive Care Unit, Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland.

We evaluated the effects of different respiratory assist modes on cerebral blood flow (CBF) and arterial oxygenation in single-ventricle patients after bidirectional superior cavopulmonary anastomosis (BCPA). We hypothesized that preserved auto-regulation of respiration during neurally adjusted ventilatory assist (NAVA) may have potential advantages for CBF and pulmonary blood flow regulation after the BCPA procedure. We enrolled 23 patients scheduled for BCPA, who underwent pressure-controlled ventilation (PCV), pressure support ventilation (PSV), and NAVA at two assist levels for all modes in a randomized order. PCV targeting large V T (15 mL × kg(-1)) resulted in lower CBF and oxygenation compared to targeting low V T (10 mL × kg(-1)). During PSV and NAVA, ventilation assist levels were titrated to reduce EAdi from baseline by 75 % (high assist) and 50 % (low assist). High assist levels during PSV (PSVhigh) were associated with lower PaCO2, PaO2, and O2SAT, lower CBF, and higher pulsatility index compared with those during NAVAhigh. There were no differences in parameters when using low assist levels, except for slightly greater oxygenation in the NAVAlow group. Modifying assist levels during NAVA did not influence hemodynamics, cerebral perfusion, or gas exchange. Targeting the larger V T during PCV resulted in hyperventilation, did not improve oxygenation, and was accompanied by reduced CBF. Similarly, high assist levels during PSV led to mild hyperventilation, resulting in reduced CBF. NAVA's results were independent of the assist level chosen, causing normalized PaCO2, improved oxygenation, and better CBF than did any other mode, with the exception of PSV at low assist levels.
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http://dx.doi.org/10.1007/s00246-016-1392-9DOI Listing
August 2016

Iloprost for children with pulmonary hypertension after surgery to correct congenital heart disease.

Pediatr Pulmonol 2015 Jun 9;50(6):588-95. Epub 2014 Mar 9.

Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Congenital heart disease (CHD) can cause pulmonary hypertension (PH) in children, and surgery to correct CHD may be complicated by postoperative pulmonary hypertensive crises (PHC). Clinical data regarding the use of inhaled iloprost to treat children with PH are scarce. Our aim was to determine the efficacy and safety of iloprost in children with PH following surgery to correct CHD. This was a randomized, placebo-controlled study of 22 children (median age 7 months) undergoing surgery to achieve biventricular repair. The combined clinical endpoint was a decrease of more than 20% in the ratio of systolic pulmonary arterial pressure to systolic arterial pressure or pulmonary resistance to systemic resistance, with no PHC or death. Patients were randomized to receive low-dose iloprost (30 ng/kg/min), high-dose iloprost (50 ng/kg/min), or placebo, for 10 min every 2 hr in the first 48 hr after surgery. PHC were experienced by two patients who received placebo and one patient treated with high-dose iloprost. The combined clinical endpoint was reached by six patients administered low-dose iloprost (P = 0.005) and four administered high-dose iloprost (P = 0.077), compared with none in the placebo group. Patients treated with iloprost showed a significant reduction from baseline in mean pulmonary vascular resistance index (-2.2 Wood units, P < 0.05), whereas patients who received placebo showed no significant change. This study supports the use of iloprost to treat children with PH following surgery to correct CHD.
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http://dx.doi.org/10.1002/ppul.23032DOI Listing
June 2015

Elevated plasma B-type natriuretic peptide and C-reactive protein levels in children with restrictive right ventricular physiology following tetralogy of Fallot repair.

Congenit Heart Dis 2014 Nov-Dec;9(6):521-8. Epub 2014 Feb 13.

Cardiac Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: This study aimed to compare the levels of plasma B-type natriuretic peptide (BNP) and C-reactive protein (CRP) in relation to oxygen transport between patients with restrictive right ventricle (rRV) and those without (non-rRV) early after tetralogy of Fallot (TOF) repair.

Methods: Eighty patients (30 in the rRV group) underwent TOF repair in 2011 and 2012. BNP and CRP were repeatedly measured during postoperative day (POD) 7, along with oxygen transport variables including arterial and superior vena cava oxygen saturation (SaO2 and SvO2 ), oxygen extraction ratio (ERO2 ), and lactate. Demographic data included age and durations of cardiopulmonary bypass (CPB), aortic cross-clamping (ACC), mechanical ventilation, and ICU and hospital stays.

Results: During POD 7, BNP did not change in either of the two groups but was consistently higher in the rRV group (P < .0001). CRP increased from POD 1 to POD 2 and decreased thereafter. The decrease was slower in the rRV group (P = .04). The increase in SvO2 and the decrease in ERO2 were slower in the rRV group (P < .05). Lactate decreased in both groups (P < .05) but was consistently higher in the rRV group (P = .03). BNP was negatively correlated with SvO2 and preoperative SaO2 and positively correlated with ERO2 and lactate (P < .05). No correlation was found between CRP and oxygen transport variables. The rRV group was older and required longer CPB, ACC, mechanical ventilation, and ICU and hospital stays compared with the non-rRV group (P < .05 for all).

Conclusions: rRV physiology is associated with significantly higher BNP and CRP levels with poorer balance of systemic oxygen transport. Information about these pathophysiological changes may help to identify appropriate treatment strategies in this difficult group of patients.
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http://dx.doi.org/10.1111/chd.12166DOI Listing
August 2015

Improvement of the depth resolution in depth-resolved wavenumber-scanning interferometry using multiple uncorrelated wavenumber bands.

Appl Opt 2013 Jul;52(20):4890-7

Faculty of Automation, Guangdong University of Technology, Guangzhou, Guangdong, China.

In this article, we provide a method to improve the depth resolution of wide-field depth-resolved wavenumber-scanning interferometry (DRWSI), because its depth resolution is limited by the range of the wavenumber scanning and mode hopping of the light source. An optical wedge is put into the optical path to measure the series of the wavenumber on time using a 2D spatial Fourier transform (FT) of the interferograms. Those uncorrelated multiple bands of the wavenumbers due to mode hopping of the diode laser can be synthesized into one band, to enlarge the range of the wavenumber scanning. A random-sampling FT is put forward to evaluate the distribution of frequencies and phases of the multiple surfaces measured. The benefit is that the depth resolution of the DRWSI is enhanced significantly with a higher signal-to-noise ratio. Because of its simplicity and practicability, this method broadens the way to employing multiple different lasers or lasers with mode hopping as the light sources in the DRWSI.
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http://dx.doi.org/10.1364/AO.52.004890DOI Listing
July 2013

Beneficial effect of exogenous surfactant in infants suffering acute respiratory distress syndrome after cardiac surgery.

Eur J Cardiothorac Surg 2011 Sep 2;40(3):557-62. Epub 2011 Mar 2.

Department of Cardiovascular and Thoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: The efficiency of exogenous pulmonary surfactant for pediatric patients suffering acute respiratory distress syndrome after cardiac surgery remains indeterminate. This study explored (1) whether use of exogenous surfactant improved recovery for patients suffering postoperative acute respiratory distress syndrome and (2) whether kinetic analysis of pulmonary functional change was helpful to indicate an appropriate dosing scheme.

Methods: Pediatric patients receiving an exogenous surfactant due to acute respiratory distress syndrome after cardiac surgery for congenital heart defects were reviewed from chart records. They were compared with patients without its use despite the same postoperative complication. Oxygenation index and ventilation index were calculated and fitted with a monoexponential function before and after its use. Other outcomes including chest radiography, duration of mechanical ventilation, and intensive care unit and hospital stay were also analyzed.

Results: All patients developing postoperative acute respiratory distress syndrome were infants. Among them, 19 infants received surfactant administration (Curosurf, 100 mg kg⁻¹, treatment group). Twenty-four infants without its administration served as control, though also suffering from the same complication. All infants receiving surfactant survived, whereas three infants in the control group died. The duration of mechanical ventilation or hospital stay was significantly shorter after surfactant administration. The infants received either one (n = 13, one-dose subgroup) or two doses (n = 6, two-dose subgroup) before successful weaning from the ventilator. After the first dose was administered, the maximal rates of oxygen index and ventilation index change were significantly higher for infants in the one-dose subgroup (oxygen index: 2.3 ± 0.9 vs 0.8 ± 0.7, p = 0.009, ventilation index: 12.9 ± 3.8 vs 3.9 ± 2.5, p = 0.007). Shortly thereafter (< 12 h), both parameters in the two-dose subgroup deteriorated and a second dose was administered 24h later.

Conclusions: Exogenous pulmonary surfactant is an efficient medication for infants suffering acute respiratory distress syndrome after cardiac surgery. Kinetics analysis of functional change after initial surfactant use may be referred for early determination of an optimal dosing scheme.
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http://dx.doi.org/10.1016/j.ejcts.2011.01.008DOI Listing
September 2011

Peri-operative pulmonary hypertension in paediatric patients: current strategies in children with congenital heart disease.

Cardiology 2010 24;116(1):10-7. Epub 2010 Apr 24.

Department of Paediatric Cardiology, University Hospital Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49, Leuven, Belgium.

Congenital heart disease (CHD) is responsible for pulmonary hypertension (PH) in children in about 50% of cases. This pre-operative dynamic pulmonary hypertension can be superimposed and aggravated by acute post-operative PH or persist as chronic PH, especially in children who are not operated on early enough. Inhaled iloprost, a stable prostacyclin analogue, is used for the post-operative management of PH in infants and children with CHD. In a prospective open-label proof-of-concept study, the efficacies of inhaled nitric oxide (iNO) and inhaled iloprost were directly compared. Primary endpoints were the occurrence of a major or minor pulmonary hypertensive crisis. No significant difference between the effects of iNO versus iloprost on peri-operative PH was observed. Neither substance on its own prevented pulmonary hypertensive crises in high-risk infants, so a combination of both substances should be tested in future trials. In China, there are more than 4 million untreated CHD patients. More than 50% of them are untreated adults. Acute pulmonary vasoreactivity tests were performed in CHD patients between 9 months and 43 years of age using inhaled iloprost, in order to find out whether a pre-operative response to inhaled iloprost is a good predictor for the post-operative performance of these patients. The results showed that patient selection criteria for surgery should include both a 20% reduction in pulmonary vascular resistance (PVR) index after iloprost inhalation and a resulting PVR index <11 Wood U/m(2). CHD children between 14 days and 11 years of age took part in a placebo-controlled pilot study that investigated the role of aerosolized iloprost in the treatment of PH after corrective surgery. They received either low- or high-dose iloprost or placebo. Inhaled iloprost significantly improved haemodynamics in a dose-dependent manner and prevented reactive PH and pulmonary hypertensive crises in most of these mechanically ventilated children after CHD repair.
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http://dx.doi.org/10.1159/000313864DOI Listing
September 2010

Nitric oxide in conjunction with milrinone better stabilized pulmonary hemodynamics after Fontan procedure.

Artif Organs 2008 Nov;32(11):864-9

Department of Cardiovascular and Thoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Inhaled nitric oxide (iNO) has been used for patients with increased pulmonary vascular resistance (PVR) shortly after Fontan operation, but repeat deterioration of PVR during or shortly after its withdrawal remains a major concern. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, can also reduce PVR for postoperative patients with pulmonary hypertension. We hypothesized that iNO, in conjunction with milrinone, can provide additive benefits for pulmonary hemodynamics and reduce the occurrence of iNO withdrawal failure/rebound. Thirty-one patients with marked elevation of transpulmonary pressure gradient (TPG, >10 mm Hg) or central venous pressure (CVP, >15 mm Hg) after modified fenestrated Fontan operation were prospectively randomized into two groups, that is, group iNO (iNO at approximately 10 ppm, n = 15) and group iNO + Mil (iNO at approximately 10 ppm and milrinone at 0.5 microg/kg/min, n = 16). Hemodynamics, arterial blood oxygenation, and occurrence of withdrawal failure/rebound were compared between the two groups. Combined application of iNO and milrinone resulted in (i) more significant decrement of CVP (19.6 +/- 3.5% in group iNO + Mil vs. 15.2 +/- 4.6% in group iNO, P < 0.05) and TPG (18.2 +/- 4.8% in group iNO + Mil vs. 15.3 +/- 2.6% in group iNO, P < 0.05), (ii) more significant increment of systolic systemic arterial pressure (8.7 +/- 2.7% in group iNO + Mil vs. 5.2 +/- 3.1% in group iNO, P < 0.05), and (iii) more significant improvement of arterial oxygen saturation (9.3 +/- 3.2% in group iNO + Mil vs. 6.8 +/- 2.8% in group iNO, P < 0.01). Occurrence of iNO withdrawal failure during its weaning or rebound after its discontinuation was significantly lower in group iNO + Mil. The combined use of iNO and milrinone provided additive benefits as compared with exclusive use of iNO for patients with elevated PVR after Fontan procedure.
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http://dx.doi.org/10.1111/j.1525-1594.2008.00643.xDOI Listing
November 2008

Nitric oxide and milrinone: combined effect on pulmonary circulation after Fontan-type procedure: a prospective, randomized study.

Ann Thorac Surg 2008 Sep;86(3):882-8; discussion 882-8

Department of Cardiovascular and Thoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (Formerly Shanghai Second Medical University), Shanghai, China.

Background: Early morbidity and mortality after Fontan operations are related to the elevation of postoperative pulmonary vascular resistance. Inhalation of nitric oxide (iNO) and intravenous milrinone are two options capable of reducing pulmonary vascular resistance. We hypothesized that their combined use could maximally stabilize the pulmonary circulation after Fontan operation.

Methods: Forty-six patients with high pulmonary vascular resistance (transpulmonary pressure gradient >10 mm Hg or central venous pressure >15 mm Hg) and impaired oxygenation after Fontan operation were prospectively randomized into three groups: group Mil (n = 15, milrinone at 0.5 microg x kg(-1) x min(-1)), group iNO (n = 15, iNO at <20 ppm), and group iNO + Mil (n = 16, iNO plus Mil). Pulmonary hemodynamic and oxygenation changes were compared among the three groups.

Results: Inhalation of nitric oxide with milrinone led to (1) the most significant reduction of pulmonary vascular resistance (transpulmonary pressure gradient from 11.26 +/- 1.40 mm Hg [baseline] to 7.93 +/- 0.90 mm Hg [24-hour use] in group iNO + Mil versus from 11.10 +/- 1.38 to 8.69 +/- 0.86 mm Hg; p = 0.048 in group iNO and from 11.17 +/- 1.41 mm Hg to 9.72 +/- 1.32 mm Hg; p < 0.001 in group Mil); (2) the most significant improvement of arterial blood oxygenation (ratio of arterial oxygen partial pressure to inspired fraction of oxygen from 68.88 +/- 14.09 to 131.25 +/- 15.92 in group iNO + Mil versus from 70.07 +/-14.24 to 120.20 +/- 15.92; p = 0.047 in group iNO and from 72.60 +/- 12.92 to 95.20 +/- 13.49; p < 0.001 in group Mil). Time on mechanical ventilation was shortest in group iNO + Mil (p = 0.043).

Conclusions: Combined use of iNO and milrinone optimally stabilized pulmonary hemodynamics after Fontan operation.
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http://dx.doi.org/10.1016/j.athoracsur.2008.05.014DOI Listing
September 2008

Autologous Ross operation for congenital aortic stenosis.

Pediatr Cardiol 2006 Nov-Dec;27(6):750-4. Epub 2006 Oct 9.

Department of Pediatric Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Second Medical University, Shanghai, China.

Congenital aortic stenosis is a relatively common cardiac anomaly encountered in approximately 5% of all children with heart disease. The Ross procedure is increasingly used for replacement of the aortic valve in children. We report a 12-year-old boy who was born with congenital aortic stenosis secondary to a bicommissural aortic valve. The patient underwent open valvotomy in infancy and aortic valvuloplasty 2 years later. Residual/recurrent stenosis prompted referral for aortic valve replacement, and he underwent an autologous Ross procedure, in which the aortic root was replaced with a pulmonary autograft and the repaired aortic valve was used to restore right ventricular-to-pulmonary artery continuity. The postoperative course was unremarkable. Nitroprusside, esmolol, and labetolol were used to control postoperative hypertension. He was discharged 4 days after surgery on oral furosemide and aspirin, and he has had no cardiovascular symptoms during follow-up. Recent echocardiography demonstrated mild right ventricular outflow tract obstruction with a peak velocity of 3.6 m/sec, with a gradient of 42 mmHg and moderate pulmonary insufficiency. There was no left ventricular outlet tract obstruction or aortic insufficiency.
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http://dx.doi.org/10.1007/s00246-006-1060-6DOI Listing
March 2007
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