1.LncRNA-UCA1-microRNA-143-Notch1 regulates autophagy in myocardial ischemia reperfusion injury induced by cardiopulmonary bypass.
Lingzhi JIANG ; Mingshan WANG ; Ye SHEN
Chinese Critical Care Medicine 2025;37(6):576-582
OBJECTIVE:
To observe the degree of myocardial cell injury and the changes in autophagy level in rats with myocardial ischemia/reperfusion (I/R) injury induced by cardiopulmonary bypass (CPB), and to explore the regulatory role of the long non-coding RNA-urothelial carcinoma antigen 1-microRNA-143-Notch1 axis (lncRNA-UCA1-miR-143-Notch1 axis) in myocardial I/R injury induced by CPB.
METHODS:
Healthy male Sprague-Dawley (SD) rats were randomly divided into the following groups using the random number method: Sham operation (Sham) group, myocardial I/R injury model group (model group), empty lentivirus group, lncRNA-UCA1 upregulation group, miR-143 downregulation group, and lncRNA-UCA1 upregulation+miR-143 upregulation group, with 9 rats in each group. The rat model of myocardial I/R injury induced by CPB was established by thoracotomy aortic ligation under cardiopulmonary bypass support; in the Sham group, only threading was performed without ligation, and other procedures were the same. Seventy-two hours before modeling, the lncRNA-UCA1 upregulated group was injected with 100 μL of myocardial tissue-specific adeno-associated virus (AAV) overexpression vector of lncRNA-UCA1 via tail vein, the miR-143 downregulated group was injected with 100 μL of AAV short hairpin RNA (shRNA) vector of miR-143 via tail vein, the lncRNA-UCA1 upregulation+miR-143 upregulation group was injected with 100 μL of myocardial tissue-AAV overexpression vector of lncRNA-UCA1 and 100 μL of AAV overexpression vector of miR-143 via tail vein, and the empty vector lentivirus group was injected with 100 μL of AAV empty vector (virus titers were 1×109 TU/mL); the Sham group and the model group were injected with equal amounts of normal saline. The animals were euthanized 24 hours after intervention and cardiac tissue specimens were collected. After hematoxylin eosin (HE) staining, the damage of myocardial cells and the changes of muscle fiber tissue were observed under a light microscope; after dual staining with uranyl acetate and lead citrate, the ultrastructural damage of heart tissue was observed under a transmission electron microscopy; the expression of lncRNA-UCA1, miR-143, and Notch1 mRNA in myocardial tissue was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR); the expression of microtubule 1 light chain 3-II/I (LC3-II/I) and Notch1 protein in myocardial tissue was detected by Western blotting.
RESULTS:
Compared with the Sham group, the myocardial cells of rats in the model group were enlarged, the intercellular space increased, autophagosomes increased, the arrangement of myocardial fibers was disordered, mitochondrial proliferated and deformed. The expression levels of lncRNA-UCA1 and Notch1 mRNA, as well as the protein expression levels of LC3-II/I and Notch1 were significantly increased, while the expression level of miR-143 was significantly decreased. Compared with the model group, the degree of myocardial cell injury in the lncRNA-UCA1 upregulation group and miR-143 downregulation group was significantly alleviated, the expression levels of Notch1 mRNA, LC3-II/I, and Notch1 protein were significantly increased [Notch1 mRNA (2-ΔΔCt): 2.66±0.24, 2.03±0.23 vs. 1.45±0.13, LC3-II/I: 2.10±0.21, 1.92±0.19 vs. 1.39±0.14, Notch1 protein (Notch1/GAPDH): 1.72±0.16, 1.57±0.16 vs. 1.34±0.13, all P < 0.05], and the expression level of miR-143 was significantly decreased (2-ΔΔCt: 0.50±0.06, 0.52±0.06 vs.0.71±0.06, P < 0.05). The expression level of lncRNA-UCA1 in the lncRNA-UCA1 upregulated group was significantly higher than that in the model group (2-ΔΔCt: 2.47±0.22 vs. 1.43±0.14, P < 0.05), while there was no significant difference in the miR-143 downregulation group compared with the model group (2-ΔΔCt: 1.50±0.16 vs. 1.43±0.14, P > 0.05). There was no significant difference in the degree of myocardial cell injury in the empty load lentivirus group and the lncRNA-UCA1 upregulation+miR-143 upregulation group compared to the model group. There were no significant differences in the expression of miR-143, Notch1 mRNA, and the autophagy level in these two groups compared to the model group. The expression level of lncRNA-UCA1 in the lncRNA-UCA1 upregulation+miR-143 upregulation group was significantly higher than that in the model group (2-ΔΔCt: 2.47±0.20 vs. 1.43±0.14, P < 0.05).
CONCLUSIONS
Autophagy is involved in the pathological process of myocardial I/R injury induced by CPB. The lncRNA-UCA1-microRNA-143-Notch1 axis may regulate the autophagy level to participate in the I/R injury process.
Animals
;
MicroRNAs
;
Rats, Sprague-Dawley
;
RNA, Long Noncoding
;
Male
;
Myocardial Reperfusion Injury/etiology*
;
Rats
;
Cardiopulmonary Bypass/adverse effects*
;
Receptor, Notch1/metabolism*
;
Autophagy
3.Elevation of C-reactive protein early after cardiopulmonary bypass surgery is associated with occurrence of postoperative atrial fibrillation.
Yong HE ; Si Yun LIU ; Yong Jin LUO ; Hong Kun WU ; Yang YU ; Hao CHEN
Journal of Southern Medical University 2022;42(3):443-447
OBJECTIVE:
To explore the association between postoperative C-reactive protein (CRP) levels and the occurrence of postoperative atrial fibrillation in patients undergoing cardiopulmonary bypass surgery.
METHODS:
We retrospectively analyzed the data of 550 patients undergoing cardiopulmonary bypass surgery in our hospital from September, 2018 to May, 2021, and after screening against the exclusion criteria, 363 patients were selected for further analysis. Univariate analysis was used to analyze the correlation of age and early postoperative CRP level with the occurrence of postoperative atrial fibrillation, and Chi-square test was used to explore the correlation of gender, disease type, and comorbidity with postoperative atrial fibrillation followed by multivariate analysis of the data using a binary logistic regression model.
RESULTS:
The 363 patients enrolled in this study included 247 with valvular disease, 42 with aortic dissection, 37 with coronary heart disease, and 37 with congenital heart disease, with a median postoperative CRP level of 88.65 mg/L and a median age of 57 years (range 5-77 years). Postoperative atrial fibrillation occurred in 101 (27.82%) of the patients, who were subsequently divided into atrial fibrillation group and sinus group. Univariate and multivariate correlation analyses showed that early postoperative elevation of CRP level was an important factor contributing to the occurrence of postoperative atrial fibrillation.
CONCLUSION
Early postoperative elevation of CRP level is associated with the occurrence of atrial fibrillation following cardiopulmonary bypass surgery.
Adolescent
;
Adult
;
Aged
;
Atrial Fibrillation/etiology*
;
C-Reactive Protein/analysis*
;
Cardiopulmonary Bypass/adverse effects*
;
Child
;
Child, Preschool
;
Coronary Artery Bypass
;
Humans
;
Middle Aged
;
Postoperative Complications/epidemiology*
;
Retrospective Studies
;
Risk Factors
;
Young Adult
4.Replacement Therapy for Hemophilia Patients Undergoing Cardiac Surgery: Report of Three Cases.
Xiaokun CHEN ; Qi MIAO ; Tie-Nan ZHU ; Chao-Ji ZHANG
Chinese Medical Sciences Journal 2022;37(1):79-81
Hemophilia is an X-linked recessive inherited bleeding disorder. Despite the improved treatment in recent years with the advent of replacement therapies, the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia. As life expectancy increases, more hemophilia patients will suffer from age-related cardiovascular diseases. Since cardiac surgery needs heparinization and cardiopulmonary bypass (CPB), it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia. Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.
Cardiac Surgical Procedures/adverse effects*
;
Cardiopulmonary Bypass
;
Hemophilia A/complications*
;
Humans
5.Clinical risk score for postoperative pneumonia following heart valve surgery.
Da-Shuai WANG ; Xiao-Fan HUANG ; Hong-Fei WANG ; Sheng LE ; Xin-Ling DU
Chinese Medical Journal 2021;134(20):2447-2456
BACKGROUND:
Postoperative pneumonia (POP) is one of the most common infections following heart valve surgery (HVS) and is associated with a significant increase in morbidity, mortality, and health care costs. This study aimed to identify the major risk factors associated with the occurrence of POP following HVS and to derive and validate a clinical risk score.
METHODS:
Adults undergoing open HVS between January 2016 and December 2019 at a single institution were enrolled in this study. Patients were randomly assigned to the derivation and validation sets at 1:1 ratio. A prediction model was developed with multivariable logistic regression analysis in the derivation set. Points were assigned to independent risk factors based on their regression coefficients.
RESULTS:
POP occurred in 316 of the 3853 patients (8.2%). Multivariable analysis identified ten significant predictors for POP in the derivation set, including older age, smoking history, chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, poor cardiac function, heart surgery history, longer cardiopulmonary bypass, blood transfusion, and concomitant coronary and/or aortic surgery. A 22-point risk score based on the multivariable model was then generated, demonstrating good discrimination (C-statistic: 0.81), and calibration (Hosmer-Lemeshow χ2 = 8.234, P = 0.312). The prediction rule also showed adequate discriminative power (C-statistic: 0.83) and calibration (Hosmer-Lemeshow χ2 = 5.606, P = 0.691) in the validation set. Three risk intervals were defined as low-, medium-, and high-risk groups.
CONCLUSION:
We derived and validated a 22-point risk score for POP following HVS, which may be useful in preventive interventions and risk management.
TRIAL REGISTRATION
Chictr.org, ChiCTR1900028127; http://www.chictr.org.cn/showproj.aspx?proj=46932.
Adult
;
Aged
;
Cardiac Surgical Procedures/adverse effects*
;
Cardiopulmonary Bypass
;
Heart Valves
;
Humans
;
Pneumonia
;
Risk Factors
6.Association of hypoalbuminemia with acute kidney injury in children after cardiac surgery.
Lian DUAN ; Guo-Huang HU ; Meng JIANG ; Cheng-Liang ZHANG ; Yan-Ying DUAN
Chinese Journal of Contemporary Pediatrics 2018;20(6):475-480
OBJECTIVETo study whether hypoalbuminemia after pediatric cardiopulmonary bypass (CPB) for cardiac surgery is a risk factor for postoperative acute kidney injury (AKI).
METHODSA retrospective analysis was performed on the clinical data of 1 110 children who underwent CPB surgery between 2012 and 2016. According to the minimum serum albumin within 48 hours postoperatively, these patients were divided into hypoalbuminemia group (≤35 g/L) and normal albumin group (>35 g/L). The two groups were compared in terms of perioperative data and the incidence of AKI. Furthermore, the incidence of AKI was compared again after propensity score matching for the unbalanced factors during the perioperative period. The perioperative risk factors for postoperative AKI were analyzed by logistic regression.
RESULTSThe overall incidence rate of postoperative AKI was 13.78% (153/1 110), and the mortality rate was 2.52% (28/1 110). The mortality rate of children with AKI was 13.1% (20/153). The patients with hypoalbuminemia after surgery (≤35 g/L) accounted for 44.50% (494/1 110). Before and after propensity score matching, the hypoalbuminemia group had a significantly higher incidence of AKI than the normal albumin group (P<0.05). The children with AKI had a significantly lower serum albumin level after surgery than those without AKI (P<0.05). The multivariate logistic regression analysis showed albumin ≤35 g/L was one of the independent risk factors for postoperative AKI.
CONCLUSIONSAlbumin ≤35 g/L within 48 hours postoperatively is an independent risk factor for postoperative AKI in children after CPB surgery.
Acute Kidney Injury ; epidemiology ; etiology ; Adolescent ; Cardiopulmonary Bypass ; adverse effects ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Heart Diseases ; surgery ; Humans ; Hypoalbuminemia ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Male ; Perioperative Period ; Postoperative Complications ; epidemiology ; etiology ; Propensity Score ; Retrospective Studies
7.Surgical Treatment of Refractory Chest Tumors Assisted by Cardiopulmonary Bypass.
Rongying ZHU ; Shanzhou DUAN ; Wentao YANG ; Li SHI ; Fuquan ZHANG ; Yongbing CHEN
Chinese Journal of Lung Cancer 2018;21(4):313-317
BACKGROUND:
A retrospective review of the surgical treatment of refractory chest tumors involving the heart or large vessels with cardiopulmonary bypass (CPB).
METHODS:
To summarize 11 cases of chest tumor patients who had undergone cardiopulmonary bypass surgery from January 2008 to May 2017 in our hospital, and analyze the general condition, clinical characteristics, treatment methods, postoperative hospitalization time, complications and follow-up results of all patients.
RESULTS:
All 11 patients were operated with cardiopulmonary bypass. Total resection of tumors in 8 cases and most of the excision in 3 cases. 1 case of left atrial metastatic leiomyosarcoma were excised in the left atrium, and then the right lung resection was performed. 1 case of left lung central lung cancer resection through the median sternum incision. 2 cases underwent pulmonary artery repair at the same time, 3 cases underwent partial pericardiectomy and 3 cases underwent pulmonary wedge resection at the same time. All the patients were effectively relieved after the operation. No death rate in hospital and 30 days after operation. 3 cases of postoperative pulmonary infection were recovered after the treatment of antibiotics. 1 case of lymphoma relapsed 6 months after surgery and died one year later. 1 case of pericardial fibrosarcoma had local recurrence and extensive metastasis at 13 months after operation, and died after 15 months. 1 case of pulmonary leiomyosarcoma were found to have local recurrence 15 months after the operation and were relieved after chemotherapy. The remaining 8 patients survived, and no obvious recurrence and distant metastasis were found in the computed tomography (CT) examination.
CONCLUSIONS
The CPB assisted surgical treatment can be performed for patient of refractory chest tumors involving the heart or large vessels. It can improve the surgical resection rate of refractory chest tumors, effectively alleviate the effects on respiratory and circulatory functions, and significantly prolong the survival period of these patients.
Adult
;
Cardiopulmonary Bypass
;
adverse effects
;
Female
;
Humans
;
Lung Neoplasms
;
diagnostic imaging
;
mortality
;
physiopathology
;
surgery
;
Male
;
Middle Aged
;
Postoperative Complications
;
etiology
;
Pulmonary Artery
;
diagnostic imaging
;
physiopathology
;
surgery
;
Retrospective Studies
8.Values of combination of urinary L-FABP and NGAL in early diagnosis of acute kidney injury after cardiac surgery in children.
Rong TANG ; Xiang AO ; Yong ZHONG ; Rui-Ling WANG ; Qiao-Ling ZHOU
Chinese Journal of Contemporary Pediatrics 2017;19(7):770-775
OBJECTIVETo investigate the values of combination of urinary liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in children.
METHODSA total of 97 children with congenital heart disease undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples were collected before and after surgery. Levels of serum creatinine (Scr), urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79) were measured, and the postoperative dynamic changes in these markers were compared between the two groups. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to assess the values of these markers alone or in combination in the prediction of postoperative AKI.
RESULTSThe levels of urinary L-FABP and NGAL in the AKI group were significantly higher than those in the non-AKI group at 2 and 6 hours after surgery, and the changes in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896 respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively. Those of their combination were 0.942 and 0.929 respectively.
CONCLUSIONSUrinary L-FABP and NGAL significantly increase in the early stage of AKI after cardiac surgery in children, which are significantly earlier than the changes in Scr. They can be used to predict the occurrence of AKI in the early stage. A combination of the two biomarkers can further improve the accuracy of diagnosis.
Acute Kidney Injury ; diagnosis ; urine ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Creatinine ; blood ; Fatty Acid-Binding Proteins ; urine ; Female ; Humans ; Infant ; Lipocalin-2 ; urine ; Male
9.Effect of Stellate Ganglion Block on Bilateral Regional Cerebral Oxygen Saturation and Postoperative Cognitive Function.
Yuan ZHANG ; Yanning QIAN ; Hongguang BAO ; Hongwei SHI ; Jianwei ZHOU
Journal of Biomedical Engineering 2016;33(1):132-135
The present study was to examine the effect of stellate ganglion block (SGB) on bilateral regional cerebral oxygen saturation (rSO2) and postoperative cognitive function. Eighty patients undergoing selective coronary artery bypass graft with cardiopulmonary bypass (CPB) were randomly and equally divided into two groups. The patients in group S were given right SGB with ropivacaine, while the patients in group C were injected with normal saline. We compared the bilateral rSO2 after SGB. Minimum Mental State Examination (MMSE), Visual Verbal Learning Test (VVLT), and Digital Span Test (DST) were applied to observe the effect on cognitive function. We found that the incidence of postoperative cognitive dysfunction (POCD) 7 days after surgery in group S was lower than that in group C. The level of blocked side rSO₂ of S group were significantly higher before CPB time of rewarming than that before SGB (P < 0.05), much higher than corresponding non-blocked side rSO₂ before CPB (P < 0.05), and much higher than rSO₂ level in group C before CPB and after CPB (P < 0.05). The non-blocked side rSO₂ in group S before anesthesia were much lower than basic levels and those in group C (P < 0.05). It could be concluded from the above results that there was significant increase in the blocked-side rSO₂ compared to the non-blocked side and there was significant decrease in the incidence of POCD compared to the control group after SGB.
Autonomic Nerve Block
;
adverse effects
;
Cardiopulmonary Bypass
;
adverse effects
;
Cerebrum
;
physiology
;
Cognition
;
Cognition Disorders
;
Coronary Artery Bypass
;
adverse effects
;
Humans
;
Incidence
;
Oxygen
;
physiology
;
Oxygen Consumption
;
Postoperative Complications
;
Stellate Ganglion
10.Lack of Efficacy of Ulinastatin Therapy During Cardiopulmonary Bypass Surgery.
Yan QIU ; Jing LIN ; Yang YANG ; Jing ZHOU ; Li-Na GONG ; Zhen QIN ; Lei DU
Chinese Medical Journal 2015;128(23):3138-3142
BACKGROUNDIt was believed that inflammatory response induced by cardiopulmonary bypass (CPB) was blamed for complications after cardiac surgery. To improve the outcome, many pharmacological interventions have been applied to attenuate inflammatory response during CPB. The objective of this study was to investigate the effect of ulinastatin (urinary trypsin inhibitor [UTI]) on outcome after CPB surgery.
METHODSTotally, 208 patients undergoing elective valves replacement between November 2013 and September 2014 were divided into Group U (n = 70) and Group C (n = 138) based on they received UTI or not. Categorical variables were compared between groups using Fisher's exact test, and continuous variables using unpaired Student's t-test or Mann-Whitney U-test. One-way analysis of variance and Dunnett's or Tukey's tests were used to compare values at different time points within the same group. The risk of outcomes was estimated and adjusted by multivariable logistic regression, propensity scoring, and mixed-effect models for all measured variables.
RESULTSBoth the serious complications in total, including death, acute lung injury, acute respiratory distress syndrome and acute kidney injury, and the other complications, including hemodialysis, infection, re-incubation, and tracheotomy were similar between the two groups (P > 0.05). After adjusted by multivariable logistic regression and the propensity score, UTI still cannot be found any benefit to improve any outcomes after cardiac surgery. Also, no statistical differences with regard to duration of postoperative mechanical ventilation, the length of Intensive Care Unit and hospital stays (P > 0.05).
CONCLUSIONUTI did not improve postoperative outcomes in our patients after cardiopulmonary bypass surgery.
Acute Kidney Injury ; etiology ; Adult ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; adverse effects ; Female ; Glycoproteins ; therapeutic use ; Humans ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies

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