Early Prone Position Ventilation in the Efficacy for Severe Hypoxemia and Neurological Complications Following Acute Type A Aortic Dissection (TAAD) Surgery.

OBJECTIVE: To analyze the efficacy of early prone position ventilation in the treatment of severe hypoxemia after surgery for acute type A aortic dissection (TAAD). METHODS: The patients were divided into a control group and a treatment group. Parameters assessed included blood gas analysis indicators [arterial oxygen partial pressure (PaO2). RESULTS: (1) Blood gas analysis: Before treatment, there was no significant difference in PaO2, SpO2, and OI levels between the two groups; after treatment, the PaO2, SpO2, and OI levels in both groups significantly increased compared to pre-treatment, with a more pronounced improvement in the treatment group than in the control group (p < 0.05). (2) Hemodynamics: Before treatment, there was no significant difference in MAP and HR levels between the two groups; after treatment, the MAP levels increased significantly in both groups compared to pre-treatment, while HR levels decreased significantly, with no significant difference between the groups. (3) Prognosis recovery: MV time, ICU stay, and total hospital stay were significantly lower in the treatment group than in the control group; the 30-day mortality rate was 14.58% in the control group and 12.50% in the treatment group, with no significant difference in 30-day mortality rate between the groups. CONCLUSION: Early prone position ventilation has shown promising application in the treatment of severe hypoxemia after TAAD surgery. Compared to traditional supine position ventilation, the use of early prone position ventilation can further improve blood gas analysis indicators in patients, and shorten MV time, ICU stay, and total hospital stay, thereby accelerating patient recovery.

Fusobacterium nucleatum predicts a high risk of metastasis for esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC. RESULTS: Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P = 0.039) and clinical stage (P = 0.0039). The WES data showed that COL22A1, TRBV10-1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis. CONCLUSION: F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC.

Exploration and validation of hub genes and pathways in the progression of hypoplastic left heart syndrome via weighted gene co-expression network analysis.

BACKGROUND: Despite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome. METHODS: Differentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein-protein interaction networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls. RESULTS: We identified 88 and 41 DEGs in LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r = 0.79 and p value = 2e-04) and pink module (r = 0.84 and p value = 4e-05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (including Fbn1, Itga8, Itga11, Itgb5 and Thbs2), and five hub genes (including Cblb, Ccl2, Edn1, Itgb3 and Map2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset. CONCLUSIONS: Our findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.

Prenatal diagnosis of a right coronary artery to right atrial fistula with a giant coronary artery aneurysm: A case report.

Coronary artery fistula (CAF) is a rare cardiac anomaly. Here, we diagnosed a right coronary artery-right atrium fistula with giant coronary artery aneurysm (CAA) via fetal echocardiography at 35 weeks' gestation. An urgent caesarean delivery was performed at 36 weeks' gestation because CAA caused mitral obstruction, and fetal atrial flutter was present. Following delivery, we performed aneurysm ligation because the new-born developed atrial tachycardia. The intraoperative findings confirmed the sonographic findings. To the best of our knowledge, prenatal ultrasound diagnosis of CAF and giant CAA has not been reported in the literature. We focus on the ultrasonic characteristics and differential diagnosis in this literature.

Three-dimensional printing enhances preparation for repair of double outlet right ventricular surgery.

OBJECTIVE: To assess the clinical value of three-dimensional (3D) printing technology for treatment strategies for complex double outlet right ventricle (DORV). METHODS: Twenty-five patients with complex double outlet right ventricle were enrolled in this study. The patients were divided into two groups: 3D printing group (eight patients) and a non-3-D printing control group (17 patients). The cardiac images of patients in the 3D printing group were transformed to Digital Imaging and Communications and were segmented and reconstructed to create a heart model. No cardiac models were created in the control group. A Pearson coefficient analysis was used to assess the correlation between measurements of 3D printed models and computed tomography angiography (CTA) data. Pre-operative assessment and planning were performed with 3D printed models, and then operative time and recovery time were compared between the two groups. RESULTS: There was good correlation (r = 0.977) between 3D printed models and CTA data. Patients in the 3D printing group had shorter aortic cross-clamp time (102.88 vs 127.76 min, P = 0.094) and cardiopulmonary bypass time (151.63 vs 184.24 min; P = 0.152) than patients in the control group. Patients with 3D printed models had significantly lower mechanical ventilation time (56.43 vs 96.76 h, P = 0.040) and significantly shorter intensive care unit time (99.04 vs 166.94 h, P = 0.008) than patients in the control group. CONCLUSIONS: 3D printed models can accurately demonstrate anatomic structures and are useful for pre-operative treatment strategies in DORV.

Perventricular device closure of doubly committed sub-arterial ventricular septal defects via a left infra-axillary approach.

BACKGROUND: This study sought to evaluate the feasibility, safety, and efficacy of perventricular device closure of a doubly committed sub-arterial ventricular septal defect (dcVSD) through a left infra-axillary approach. METHOD: Forty-five patients, with a dcVSD of less than 8 mm in diameter, were enrolled in this study. The pericardium was exposed and opened through a left infra-axillary mini-incision. Two parallel purse-string sutures were placed on the right ventricle outflow tract and under transesophageal echocardiography guidance, a delivery sheath loaded with the device was inserted into the right ventricle and advanced through the defect into the left ventricle. The device, connected to a delivery cable, was then deployed. RESULTS: Forty-one patients achieved successful device closure. In four patients, the device failed to occlude the VSD due to device dislodgement, device-related aortic regurgitation, and residual shunts, and open surgical repair was required. The mean dcVSD diameter was 4.5 ± 1.0 mm (range, 3.0-8.0 mm). The implanted device size was 6.0 ± 1.5 mm (range, 4-10 mm). All patients were implanted with an eccentric device. The mean intracardiac manipulation time was 20.9 ± 7.1 min (range, 9-45 min). The procedure time was 62.5 ± 19.5 min (range 34-105 min). There were no severe adverse events. CONCLUSIONS: Perventricular device closure of a dcVSD through a left infra-axillary approach is feasible, safe, and efficacious in selected patients with dcVSD.

Transjugular closure of secundum atrial septal defects.

OBJECTIVE: This study reports the results of a steerable delivery system under the guidance of transesophageal echocardiography (TEE) for the treatment of transjugular closure of secundum atrial septal defects (ASD). METHODS: From July 2015 to May 2016, 33 patients underwent transjugular closure of a secundum ASD under general anesthesia with TEE guidance. The right internal jugular vein was punctured and a FuStar™ steerable sheath was implanted into the right atrium and aligned vertically with the septum, and a closure device was deployed to close the defect. RESULTS: Thirty-two patients with an ASD were successfully occluded; one patient required ASD closure on cardiopulmonary bypass. Procedure time ranged from 5 to 15 (8.2 ± 3.8) min. The length of stay was three to five days after the operation. The follow-up time ranged from 1.1 to 11.0 (5.5 ± 1.5) months. There was no valve regurgitation, no malignant arrhythmias, no device dislocation, or other serious complications. CONCLUSIONS: A steerable delivery system under the guidance of TEE is a safe, effective, and cosmetic method for the transjugular closure of secundum ASDs.

Application of Real-Time Three-Dimensional Echocardiography to Evaluate the Pre- and Postoperative Right Ventricular Systolic Function of Patients with Tetralogy of Fallot.

UNLABELLED: Tetralogy of Fallot (ToF) can be challenging for clinicians to both diagnose and treat, given the multiple heart defects that are by definition associated with the illness. This study investigates the value of real-time three- dimensional echocardiography (RT-3DE) in evaluating the pre-and postoperative right ventricular systolic function of patients with tetralogy of Fallot. A total of 41 ToF patients were divided into two groups: the child group (CG) and the adult group (AG) according to age. The right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and the right ventricular ejection fraction (RVEF) of ToF patients were measured before surgery, 7 days, and 3 months after the surgery. The correlation between the preoperative Nakata index and RVEF was then analyzed. Compared with the RVEDV and RVESV prior to surgery, those of the postoperative 7-day and 3-month were not statistically significant (p > 0.05). However, RVEF decreased, and the difference was statistically significant (p < 0.05). The differences in RVEDV, RVESV, and RVEF between postoperative 3-month and 7-day were not significant (p > 0.05). Compared with the pre-and postoperative RVEDV and RVESV of CG, those of AG increased. However, RVEF decreased, and the differences were statistically significant (p < 0.05). Our study indicated that the correlation between preoperative Nakata index and RVEF was good. Ultimately, we did confirm that RT-3DE can quantitatively evaluate the right ventricular volume and systolic function of ToF patients, thereby providing clinical significance in determining postoperative efficacy and prognosis evaluation. KEY WORDS: Echocardiography; Right; Tetralogy of Fallot; Three-dimensional; Ventricular function.

Engineering of MSCs sheet for the prevention of myocardial ischemia and for left ventricle remodeling.

Tissue engineering combines cell biology and material science to construct tissues or organs for disease modeling, drug testing, and regenerative medicine. The cell sheet is a newly developed tissue engineering technology that has brought about scaffold-free tissue and shows great application potential. In this review, we summarized recent progress and future possibilities in preclinical research into and clinical applications of cell sheets fabricated by differing cell types from various sources for cardiac tissue repair, and the manufacturing strategies and promising application potential of 3D cell-dense tissue constructed from cell sheets. Special attention was paid to the mechanisms of mesenchymal stem cell (MSC) sheets in the prevention of myocardial ischemia and left ventricle remodeling. Comparing MSCs sheets with other types of cell sheets and 3D cardiac tissues, engineering tissues' potential safety and effectiveness concerns were also discussed.

Peratrial device closure of perimembranous ventricular septal defects via a small right subaxillary incision: Midterm results in patients <12 months of age.

BACKGROUND: Both percutaneous and perventricular device closures of perimembranous ventricular septal defects (Pm-VSDs) are alternatives to surgical procedures，but they all present certain drawbacks. OBJECTIVE: To report our clinical experiences and midterm follow-up results of minimally invasive peratrial device closure of Pm-VSDs under the guidance of transesophageal echocardiography(TEE) in patients <12 months of age. METHODS: Between January 2015 and December 2020，268 patients <12 months of age with Pm-VSDs underwent peratrial device closure in our institute. The procedure was performed under TEE guidance via a small right subaxillary incision. The delivery pathways is established by manipulating the hollow probe, and then the device is installed. RESULTS: A total of 263 cases (98.1%) underwent successful closure, whereas five cases failed and were converted to cardiopulmonary bypass operation via the original incision during the procedure. The mean age was 9.5 ± 2.0 months and the mean body weight was 8.8 ± 1.4 kg. The mean diameter of the VSD was 4.4 ± 0.5 mm. One patient (0.4%) underwent a second thoracotomy for postoperative intercostal hemorrhage on the second day after surgery. The mean diameter of the occluder size was 5.5 ± 0.6 mm. During the follow-up (4.3 ± 1.4 y), there was no mortality, no new aortic valve regurgitation and atrioventricular block. CONCLUSION: Peratrial device closure of Pm-VSDs via the right subaxillary route under TEE guidance is safe and effective at midterm follow-up, confirming this is an valuable alternative method for patients <12 months of age.

In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve.

BACKGROUND: Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. METHODS: Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University. RESULTS: 3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001). CONCLUSIONS: In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

Favorable mid-term performance of fully biodegradable implantable device for ventricular septal defect closure.

Objectives: To assess the mid-term safety and efficacy of transthoracic perimembranous ventricular septal defect (Pm-VSD) closure using a new biodegradable device. Implantation entailed right subaxillary minithoracotomy under transesophageal echocardiography guidance. Methods: Between October 2019 and January 2020, 13 patients (males, 5; mean age, 3.6 ± 2.5 years) with Pm-VSDs underwent transthoracic device closures at Zhengzhou University Central China Fuwai Hospital as described previously. Delivery pathways were established by manipulating a hollow probe from right atrium through tricuspid valve to right ventricle and then through VSDs to left ventricle, whereupon installation took place. Results: All occluder implantations were successfully executed. Mean defect size was 4.1 ± 1.0 mm, and mean device waist size was 5.2 ± 1.1 mm. One patient (7.7%) with 1.5-mm residual shunt showed complete closure at discharge. There was 1 instance of postoperative incomplete right bundle branch block, which converted to complete right bundle branch block at month 1. During patient follow-up (mean, 24.6 ± 0.8 months), no device dislocations, new residual shunts, new valvular regurgitation, or detectable atrioventricular block ensued. Conclusions: Closure of Pm-VSDs using a novel, fully biodegradable occluder in the manner described has proven safe and effective at mid-term follow-up. Long-term safety and efficacy of this device must be further corroborated in a large patient cohort going forward.

Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing.

Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient-parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case-control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

Transcatheter closure of perimembranous ventricular septal defect using a novel fully bioabsorbable occluder: multicenter randomized controlled trial.

Although the use of bioabsorbable occluder is expected to reduce the risk of metal occluder-related complications, it has not been approved due to incomplete degradation and new complications. Novel fully bioabsorbable occluders were designed to overcome such limitations. The aim of this study was to investigate the efficacy and safety of a fully biodegradable occluder in patients with ventricular septal defects. 125 patients with perimembranous ventricular septal defect (VSD) larger than 3 mm were screened from April 2019 to January 2020 in seven centers. 108 patients were enrolled and randomized into the bioabsorbable occluder group (n = 54 patients) and nitinol occluder group (n = 54). A non-inferiority design was utilized and all patients underwent transcatheter device occlusion. Outcomes were analyzed with a 24-month follow-up. All patients were successfully implanted and completed the trial. No residual shunt >2 mm was observed during follow-up. Transthoracic echocardiography showed a hyperechoic area corresponding to the bioabsorbable occluder which decreased primarily during the first year after implantation and disappeared within 24 months. Postprocedural arrhythmia was the only occluder-related complication with an incidence of 5.56% and 14.81% for the bioabsorbable and nitinol groups, respectively (P = 0.112). The incidence of sustained conduction block was lower in the bioabsorbable occluder group (0/54 vs. 6/54, P = 0.036) at 24-month follow-up. In conclusion, the novel fully bioabsorbable occluder can be successfully and safely implanted under echocardiography guidance and reduce the incidence of sustained postprocedural arrythmia. The efficacy and safety of this fully biodegradable occluder are non-inferior to that of a traditional nitinol one.

First hybrid implantations of novel Salus-Valves in patients with severe pulmonary regurgitation: A case series.

With the increasing age of patients after right ventricular outflow tract (RVOT) reconstruction, progressive pulmonary valve (PV) dysfunction can result in different degrees of right heart insufficiency, and PV replacement is frequently needed during follow-up. The traditional redo thoracotomy is difficult and associated with higher risks when compared to transcatheter implantations. Herein, we report the advantages and describe the outcomes of the first hybrid implantations of the novel Salus-Valves (Balance Medical, Beijing, China) from the sub-xiphoid approach in five patients (mean age of 22.6 years) with severe pulmonary regurgitation (PR) after RVOT reconstruction.

Preoperative sedation in children with congenital heart disease: 50% and 95% effective doses, hemodynamic effects, and safety of intranasal dexmedetomidine.

STUDY OBJECTIVE: To determine the 50% and 95% effective doses (ED50 and ED95, respectively), hemodynamic effects, and safety of intranasal dexmedetomidine for preoperative sedation in pediatric patients with congenital heart disease (CHD) with a left-to-right shunt. DESIGN: Double-blind sequential allocation trial. SETTING: Pediatric preoperative waiting area. PATIENTS: 86 pediatric patients ASA physical status II-III scheduled for cardiac surgery, aged1-month to 6-years-old with left-to-right type CHD. INTERVENTIONS: Children were divided into three groups according to age: infants (1 month-1 year), toddlers (1-3 years), and preschoolers (3-6 years). The first patient in all groups received intranasal dexmedetomidine (2 µg/kg), using the up-and-down Dixon method, and the and the next patient's dose was dependent on the previous patient's response. MEASUREMENTS: Assessment using the Modified Observer's Assessment of Alertness/Sedation Scale and the Mask Acceptance Scale was performed before and every 5 min after treatment. Pulse oxygen saturation and heart rate were recorded at baseline, at 10-min intervals, and after admission to the operating room. Systolic pulmonary artery pressure was measured before anesthesia induction. MAIN RESULTS: The respective ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for preoperative sedation using intranasally administered dexmedetomidine were 3.1 (2.8-3.3) and 3.5 (3.3-4.0) µg/kg for infants; 3.4 (3.2-3.6) and 3.9 (3.7-4.4) µg/kg for toddlers; and 2.4 (2.2-2.6) and 2.9 (2.6-3.3) µg/kg for preschoolers. ED50 was lower for preschoolers than for toddlers (p < 0.001) and infants (p = 0.044). No obvious difference in ED50 was found between infants and toddlers. There was no significant difference in sedation onset time among the groups, and no adverse events were observed during sedation in all patients. CONCLUSIONS: Intranasal dexmedetomidine can be safety used for preoperative sedation in children with CHD and is effective for sedation when dosed appropriately. Trial registrationclinicaltrials.gov (ChiCTR2100047472); registered 20 June 2021.

Manufacture and Quality Control of Human Umbilical Cord-Derived Mesenchymal Stem Cell Sheets for Clinical Use.

Human umbilical cord-derived mesenchymal stem cell (UC-MSC) sheets have attracted much attention in cell therapy. However, the culture media and coating matrix used for the preparation of UC-MSC sheets have not been safe enough to comply with current clinical drug standards. Moreover, the UC-MSC sheet preservation systems developed before did not comply with Good Manufacturing Practice (GMP) regulations. In this study, the culture medium and coating matrix were developed for UC-MSC sheet production to comply with clinical drug standards. Additionally, the GMP-compliant preservation solution and method for the UC-MSC sheet were developed. Then, quality standards of the UC-MSC sheet were formulated according to national and international regulations for drugs. Finally, the production process of UC-MSC sheets on a large scale was standardized, and three batches of trial production were conducted and tested to meet the established quality standards. This research provides the possibility for clinical trials of UC-MSC sheet products in the development stage of new drugs and lays the foundation for industrial large-scale production after the new drug is launched.

Preclinical study of human umbilical cord mesenchymal stem cell sheets for the recovery of ischemic heart tissue.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely used due to their multipotency, a broad range of sources, painless collection, and compliance with standard amplification. Cell sheet technology is a tissue engineering methodology requiring scaffolds free, and it provides an effective method for cell transplantation. To improve the therapeutic efficacy, we combined hUC-MSCs with cell sheet technology to evaluate the safety and efficacy of hUC-MSC sheets in preclinical studies using appropriate animal models. METHODS: hUC-MSC sheets were fabricated by hUC-MSCs from a cell bank established by a standard operation process and quality control. Cytokine secretion, immunoregulation, and angiopoiesis were evaluated in vitro. Oncogenicity and cell diffusion assays of hUC-MSC sheets were conducted to verify the safety of hUC-MSCs sheet transplantation in mice. To provide more meaningful animal experimental data for clinical trials, porcine myocardial infarction (MI) models were established by constriction of the left circumflex, and hUC-MSC sheets were transplanted onto the ischemic area of the heart tissue. Cardiac function was evaluated and compared between the experimental and MI groups. RESULTS: The in vitro results showed that hUC-MSC sheets could secrete multiple cellular factors, including VEGF, HGF, IL-6, and IL-8. Peripheral blood mononuclear cells had a lower proliferation rate and lower TNF-α secretion when co-cultured with hUC-MSC sheets. TH1 cells had a smaller proportion after activation. In vivo safety results showed that the hUC-MSCs sheet had no oncogenicity and was mainly distributed on the surface of the ischemic myocardial tissue. Echocardiography showed that hUC-MSC sheets effectively improved the left ventricular ejection fraction (LVEF), and the LVEF significantly changed (42.25 ± 1.23% vs. 66.9 ± 1.10%) in the hUC-MSC transplantation group compared with the MI group (42.52 ± 0.65% vs. 39.55 ± 1.97%) at 9 weeks. The infarct ratio of the hUC-MSCs sheet transplantation groups was also significantly reduced (14.2 ± 4.53% vs. 4.00 ± 2.00%) compared with that of the MI group. CONCLUSION: Allogeneic source and cell bank established by the standard operation process and quality control make hUC-MSCs sheet possible to treat MI by off-the-shelf drug with universal quality instead of individualized medical technology.

CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy.

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.