Del Nido cardioplegia for myocardial protection in adult cardiac surgery: a systematic review and update meta-analysis.

OBJECTIVE: Although the application of del Nido cardioplegia solution (DNC) in adult cardiac surgery is accumulating, the feasibility and safety of this myocardial protection strategy in adults remains controversial. We aimed to update our previous meta-analysis to determine the myocardial protective effect of DNC versus conventional cardioplegia (CC) in adult cardiac surgery. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2020. RESULTS: Thirty-seven observational studies and four randomized controlled trials (RCTs) including 21,779 patients were identified. The DNC group was associated with decreased postoperative cardiac enzymes [troponin T (cTnT) and creatine kinase-MB (CK-MB)] [standardized mean differences (SMD): -0.59, 95% confidence interval (CI): -0.99 to -0.19, p = 0.004], cardiopulmonary bypass (CPB) time (MD: -9.31, 95% CI: -13.10 to -5.51, p < 0.00001), aortic cross-clamp (ACC) time (MD: -7.20, 95% CI: -10.31 to -4.09, p < 0.00001), and cardioplegia volume (SMD: -1.95, 95% CI: -2.46 to -1.44, p < 0.00001). Intraoperative defibrillation requirement was less in the DNC group [relative risk (RR): 0.50, 95% CI: 0.33 to 0.75, p = 0.0007]. The pooled analysis revealed no significant difference in operative mortality among the patients assigned to DNC and those undergoing CC. CONCLUSION: In adult cardiac surgery, compared to CC, myocardial protection used with DNC yield similar or better short-term clinical outcomes. More high-quality trials and RCTs reflecting long-term follow-up morbidity and mortality are required in the future to confirm these findings.

Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. METHODS: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. RESULTS: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and fluid leakage into airspaces. CONCLUSION: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.

Venovenous extracorporeal membrane oxygenation for coronavirus disease 2019 patients: A systematic review and meta-analysis.

OBJECTIVE: Although the application of venovenous extracorporeal membrane oxygenation (VV-ECMO) in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS) is accumulating, the feasibility and safety of this therapy remain controversial. We aimed to evaluate the effect of VV-ECMO in the treatment of these patients. METHODS: A comprehensive literature search was performed using PubMed, Embase, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2021. According to the inclusion and exclusion criteria, the included studies were screened, and meta-analysis was performed by R software (version 4.0.2). RESULTS: Forty-two studies including 2037 COVID-19 patients supported with VV-ECMO due to ARDS were identified. The pooled analysis revealed that 30-, 60-, and 90-day mortality among patients were respectively 46% (95% CI 37%-57%, I2 = 66%), 46% (95% CI 30%-70%, I2 = 93%), and 49% (95% CI 43%-58%, I2 = 52%), and the pooled incidence rate of in-hospital mortality, major bleeding, hemorrhagic stroke, thrombosis, pulmonary embolism, deep venous thrombosis, and renal replacement therapy were respectively 35%, 39%, 11%, 40%, 15%, 21%, and 44%. CONCLUSION: Although COVID-19 patients may have a higher risk of bleeding, hemorrhagic stroke, and acute kidney injury during ECMO therapy, the survival rate was more than half of the cases. Our data may support the application of VV-ECMO in COVID-19 patients.

Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO.

INTRODUCTION: Although venovenous extracorporeal membrane oxygenation (VV ECMO) is a reasonable salvage treatment for acute respiratory distress syndrome (ARDS), it requires sedating the patient. Sevoflurane and propofol have pulmonary protective and immunomodulatory properties. This study aimed to compare the effectiveness of sevoflurane and propofol on rats with induced ARDS undergoing VV ECMO. METHODS: Fifteen sprague-dawley (SD) rats were randomly divided into three groups: Con group, sevoflurane (Sevo) group and propofol (Pro) group. Arterial blood gas tests were performed at time pointsT0 (baseline), T1 (the time to ARDS), and T2 (weaning from ECMO). Oxygenation index (PaO2/FiO2) was calculated, and lung edema assessed by determining the lung wet:dry ratio. The protein concentration in bronchial alveolar lavage fluid (BALF) was determined by using bicinchoninic acid assay. Haematoxylin and eosin staining was used to evaluate the lung pathological scores in each group. IL-1ß and TNF-α were also measured in the BALF, serum and lung. RESULTS: Oxygenation index showed improvement in the Sevo group versus Pro group. The wet:dry ratio was reduced in the Sevo group compared with propofol-treated rats. Lung pathological scores were substantially lower in the Sevo group versus the Pro group. Protein concentrations in the BALF and levels of IL-1ß and TNF-α in the Sevo group were substantially lower versus Pro group. CONCLUSION: This study demonstrates that compared with propofol, sevoflurane was more efficacious in improving oxygenation and decreasing inflammatory response in rat models with ARDS subject to VV ECMO treatment.

Off-pump versus on-pump redo coronary artery bypass grafting: a systematic review and meta-analysis.

BACKGROUND: Redo coronary artery bypass grafting (redo CABG) is associated with increased mortality and morbidity. The aim of this study was to systematically evaluate the evidence comparing the outcomes of off-pump with on-pump redo CABG. METHODS: Studies were systematically searched and identified using PubMed, EMBASE, the Cochrane Library, and the International Clinical Trials Registry Platform (ICTRP) by two researchers independently. The primary outcome was 30-day mortality, and the secondary outcomes were in-hospital mortality, post-operative complications, completeness of revascularization, blood transfusion rate, duration of mechanical ventilation, intensive care unit and hospital stays. RESULTS: The 21 studies including 4,889 patients were enrolled in our meta-analysis. Compared with on-pump, the off-pump technique was associated with significantly reduced 30-day mortality (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.26-0.72, p = 0.001). Moreover, a notably decreased in-hospital mortality (OR = 0.55, 95% CI = 0.39-0.76, p = 0.0004) and incidence of post-operative new-onset atrial fibrillation, myocardial infarction, acute kidney injury, low cardiac output state, blood transfusion rate (OR = 0.46, 95% CI = 0.35-0.60, p < 0.00001; OR = 0.54, 95% CI = 0.38-0.78, p = 0.0007; OR = 0.51, 95% CI = 0.37-0.70, p < 0.0001; OR = 0.31, 95% CI = 0.20-0.47, p < 0.00001; OR = 0.29, 95% CI = 0.14-0.61, p = 0.001) and significantly shortened duration of mechanical ventilation, intensive care unit and hospital stays (mean difference [MD] = -8.21 h, 95% CI = -11.74 to -4.68, p < 0.00001; MD = -0.77 d, 95% CI = -0.81 to -0.73, p < 0.00001; MD = -2.24 d, 95% CI = -3.17 to -1.32, p < 0.00001) could be observed when comparing the outcomes of off-pump with on-pump redo CABG. There was nonsignificant difference between off-pump and on-pump redo CABG in completeness of revascularization. CONCLUSION: In patients undergoing redo CABG surgery, the off-pump technique was associated with decreased mortality, less post-operative complications when compared to on-pump.

In Vitro Study on the Dynamics of Blood Flow Impelled by an Alternating Current Magnetohydrodynamic Blood Pump.

Artificial hearts are effective devices to treat heart failure in clinical practice and can be divided into two categories: artificial hearts and ventricular assist devices. The goal of this work was to investigate the fluidity and biological changes of in vitro sheep blood using a novel alternating current (AC) magnetohydrodynamic blood pump (central magnetic intensity: 0.9 T, alternating current frequency of the electric motor: 0-80 Hz). Blood samples were collected from five sheep and were divided into two groups: the control group (no exposure to an external magnetic field) and the exposed group (3 h of exposure to an alternating magnetic field). The blood cell counts, changes in blood viscosity, and ultrastructural changes of the blood cells under transmission electron microscopy were investigated. This study demonstrated several findings: (i) Continuous sheep blood flow can be achieved; (ii) The blood cell counts remained unchanged after 3 h of exposure to an alternating magnetic field; (iii) Compared with the control group, the high- and low-shear viscosities of the whole blood from the sheep significantly decreased after 3 h of exposure to an alternating magnetic field (P < 0.05 and P < 0.01, respectively). Plasma viscosity was significantly reduced after exposure to high-intensity alternating magnetic fields (P < 0.001); (iv) The cytoplasm of blood cells (especially erythrocytes) became lighter in color in the exposure group compared to the control group, and "beads-on-string" aggregations of black particles appeared. This work provides detailed and reliable scientific research data for the development of this type of blood pump, which may serve as a transition to the clinical artificial heart.

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.

[Effect of high-intensity alternating magnetic field on viscosity of sheep blood].

OBJECTIVE: To explore the changes of blood viscosity in high-intensity alternating magnetic field and the mechanisms.
 Methods: Five adult sheep were randomly selected and the blood samples were placed in high-intensity alternating magnetic field. Before and after exposure, the blood samples were taken and divided into 2 groups: a control group and a magnetic field group. The blood rheology and transmission electron microscopy (TEM) were performed.
 Results: Compared to the control group, the high shear viscosity of whole blood was decreased in the magnetic field group (P<0.05); the whole blood low shear viscosity and plasma viscosity were also decreased (both P<0.01). TEM showed the changes in red blood cell morphology and the double concave disc curvature. The radian of double concave disc and cell volume in the magnetic field group was larger than those in the control group.
 Conclusion: The high intensity alternating magnetic field may affect the distribution of surface charge and molecular current in blood cells, which in turn decrease the aggregation of cells and the blood viscosity.

Single cell RNA-seq identifies a FOS/JUN-related monocyte signature associated with clinical response of heart failure patients with mesenchymal stem cell therapy.

Heart failure (HF) is a serious global health issue that demands innovative treatment approaches. In this study, we collected samples from 4 HF patients before and after MSC therapy and performed scRNA-seq. After the MSC therapy, the proportion of CD14+ monocytes decreased significantly in both the treatment response and non-response groups, with a more pronounced decrease in the treatment response group. The therapy-response and non-response group were clearly separated in the UMAP plot, while the CD14+ monocytes in the therapy-response group before and after MSC therapy were very similar, but there were significant differences in the non-response group. By further performing NMF analysis, we identified 11 subsets of CD14+ monocytes. More importantly, we identified a therapy-related CD14+ monocyte subpopulation. The predictive model based on CD14+ monocytes constructed by machine learning algorithms showed good performance. Moreover, genes such as FOS were highly enriched in the therapy-related CD14+ monocytes. The SCENIC analysis revealed potential regulatory factors for this treatment-responsive CD14+ monocytes, and FOS/JUN were identified as potential core indicators/regulators. Finally, HF patients were divided into three groups by NMF analysis, and the therapy-responsive CD14+ monocyte characteristics were differentially activated among the three groups. Together, this study identifies treatment-responsive CD14+ monocytes as a crucial biomarker for assessing the suitability of MSC therapy and determining which HF patients could benefit from it. This provides new clues for further investigating the therapeutic mechanisms of MSC therapy, offering beneficial insights for personalized treatment and improving prognosis in HF patients.

HOXA1 gene is not potentially related to ventricular septal defect in Chinese children.

The HOXA1 gene plays a fundamental role in embryonic morphogenesis. Recent studies in humans and mice have indicated that HOXA1 plays a previously unrecognized role in cardiovascular system development. Congenital heart disease (CHD), particularly ventricular septal defect (VSD), might be a clinically isolated manifestation of HOXA1 mutations. The purpose of the present study was to identify potential pathological mutations in the HOXA1 gene in Chinese children with VSD and to gain insight into the etiology of CHD. A total of 340 nonsyndromic VSD patients and 200 normal subjects were sampled. Two exons and the nearby introns of the human HOXA1 gene were amplified using polymerase chain reaction (PCR). The PCR products were purified and directly sequenced. However, no nonsynonymous mutations in the coding regions of the HOXA1 gene were observed: Only two novel synonymous mutations (c.C210T p.His70His, and c.T861A p.Arg287Arg) were found in two patients. Two previously reported single and multiple histidine-deletion variants were identified in both normal and VSD patients. To our knowledge, this is the first study to investigate the role of the HOXA1 gene in CHD. Although our results did not show any pathogenic HOXA1 mutation, our results suggest that VSD might not be a clinically isolated manifestation of HOXA1 mutations.

Effects of spinal deformities on lung development in children: a review.

Scoliosis before the age of 5 years is referred to as early-onset scoliosis (EOS). While causes may vary, EOS can potentially affect respiratory function and lung development as children grow. Moreover, scoliosis can lead to thoracic insufficiency syndrome when aggravated or left untreated. Therefore, spinal thoracic deformities often require intervention in early childhood, and solving these problems requires new methods that include the means for both deformity correction and growth maintenance. Therapeutic strategies for preserving the growing spine and thorax include growth rods, vertically expandable titanium artificial ribs, MAGEC rods, braces and casts. The goals of any growth-promoting surgical strategy are to alter the natural history of cardiorespiratory development, limit the progression of underlying spondylarthrosis deformities and minimize negative changes in spondylothorax biomechanics due to the instrumental action of the implant. This review further elucidates EOS in terms of its aetiology, pathogenesis, pathology and treatment.

Efficacy of left subclavian artery revascularization strategies during thoracic endovascular aortic repair in patients with type B dissection: A single-center experience of 105 patients.

Background: Left subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method. Methods: In this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients. Results: The treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P < 0.05). The estimated blood loss, contrast agent volume, fluoroscopic time, operation time, and limb ischemia symptoms during the follow-up were significantly different in the four groups (P < 0.05). Pairwise comparison among groups indicated that the estimated blood loss and operation time in the CSB group were the highest (adjusted P < 0.0083; P < 0.05). The contrast agent volume and fluoroscopy duration were the highest in the SBSG groups, followed by PMF, CG, and CSB groups. The incidence of limb ischemia symptoms was the highest in the PMF group (28.6%) during the follow-up. The incidence of complications (except limb ischemia symptoms) during the perioperative and follow-up periods was similar among the four groups (P > 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P < 0.05), and the CSB group had the longest follow-up. Conclusion: Our single-center experience suggested that the PMF technique increased the risk of limb ischemia symptoms. The other three strategies effectively and safely restored LSA perfusion in patients with type B aortic dissection and had comparable complications. Overall, different LSA revascularization techniques have their advantages and disadvantages.

Nontargeted and targeted metabolomics approaches reveal the key amino acid alterations involved in multiple myeloma.

PURPOSE: Multiple myeloma (MM), a kind of malignant neoplasm of clonal plasma cells in the bone marrow, is a refractory disease. Understanding the metabolism disorders and identification of metabolomics pathways as well as key metabolites will provide new insights for exploring diagnosis and therapeutic targets of MM. METHODS: We conducted nontargeted metabolomics analysis of MM patients and normal controls (NC) using ultra-high-performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) in 40 cases of cohort 1 subjects. The targeted metabolomics analysis of amino acids using multiple reaction monitoring-mass spectrometry (MRM-MS) was also performed in 30 cases of cohort 1 and 30 cases of cohort 2 participants, to comprehensively investigate the metabolomics disorders of MM. RESULTS: The nontargeted metabolomics analysis in cohort 1 indicated that there was a significant metabolic signature change between MM patients and NC. The differential metabolites were mainly enriched in metabolic pathways related to amino acid metabolism, such as protein digestion and absorption, and biosynthesis of amino acids. Further, the targeted metabolomics analysis of amino acids in both cohort 1 and cohort 2 revealed differential metabolic profiling between MM patients and NC. We identified 12 and 14 amino acid metabolites with altered abundance in MM patients compared to NC subjects, in cohort 1 and cohort 2, respectively. Besides, key differential amino acid metabolites, such as choline, creatinine, leucine, tryptophan, and valine, may discriminate MM patients from NC. Moreover, the differential amino acid metabolites were associated with clinical indicators of MM patients. CONCLUSIONS: Our findings indicate that amino acid metabolism disorders are involved in MM. The differential profiles reveal the potential utility of key amino acid metabolites as diagnostic biomarkers of MM. The alterations in metabolome, especially the amino acid metabolome, may provide more evidences for elucidating the pathogenesis and development of MM.

Dexamethasone Alleviates Myocardial Injury in a Rat Model of Acute Myocardial Infarction Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Myocardial ischemia causes myocardial inflammation. Research indicates that the venoarterial extracorporeal membrane oxygenation (VA ECMO) provides cardiac support; however, the inflammatory response caused by myocardial ischemia remains unresolved. Dexamethasone (Dex), a broad anti-inflammatory agent, exhibits a cardioprotective effect. This study aims to investigate the effect of Dex on a rat model of acute myocardial infarction (AMI) supported by VA ECMO. Male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: Sham group (n = 5), ECMO group (n = 6), and ECMO + Dex group (n = 6). AMI was induced by ligating the left anterior descending (LAD) coronary artery. Sham group only thoracotomy was performed but LAD was not ligated. The ECMO and ECMO + Dex groups were subjected to 1 h of AMI and 2 h of VA ECMO. In the ECMO + Dex group, Dex (0.2 mg/kg) was intravenously injected into the rats after 1 h of AMI. Lastly, myocardial tissue and blood samples were harvested for further evaluation. The ECMO + Dex group significantly reduced infarct size and levels of cTnI, cTnT, and CK-MB. Apoptotic cells and the expression levels of Bax, Caspase3, and Cle-Caspase3 proteins were markedly lower in the ECMO + Dex group than that in the ECMO group. Neutrophil and macrophage infiltration was lower in the ECMO + Dex group than in the ECMO group. A significant reduction was noted in ICAM-1, C5a, MMP-9, IL-1ß, IL-6, and TNF-α. In summary, our findings revealed that Dex alleviates myocardial injury in a rat model of AMI supported by VA ECMO.

Postoperative changes in rib cage deviation in adolescent idiopathic scoliosis.

BACKGROUND: Scoliosis causes changes in the thorax, but it is unclear what type of changes occur in the thoracic profile after scoliosis surgery. OBJECTIVE: To investigate changes in rib cage deviation in the postoperative period after adolescent idiopathic scoliosis (AIS) surgery. METHODS: Forty-four patients with AIS with a main right thoracic curvature underwent posterior surgical fusion (PSF), and radiological parameters of the spine and thorax were evaluated. RESULTS: The correction rates of main thoracic curve (MT)-Cobb angle at immediate after surgery and postoperative follow-up (2 years) were 64% and 66%, respectively. At these two postoperative time points, the correction rates of height of thoracic vertebrae 1 to 12 (T1T12) were 10% and 12%; the correction rates of Rib-vertebra angle difference (RVAD) were 59% and 52%; the correction rates of Apical rib hump prominence (RH) were 58% and 76%; while the correction rates of Apical vertebral body-rib ratio (AVB-R) were 23% and 25%, respectively. Statistical analysis showed that all these radiological parameters at the two postoperative time points were significantly different from the preoperative values (p< 0.001). There were significant correlations between MT-Cobb angle and T1-T12 height (p< 0.001), RVAD (p< 0.001), RH (p< 0.001), and AVB-R (p< 0.001). CONCLUSIONS: Posterior spinal fusion appears to be effective at correcting scoliosis, and the correction of rib cage deviation also plays an important role.

Transthoracic minimally invasive closure for the treatment of ruptured sinus of Valsalva aneurysm: immediate and mid-term follow-up results.

BACKGROUND: We aimed to evaluate the immediate and mid-term outcomes of transthoracic minimally invasive closure (TMIC) of ruptured sinus of Valsalva aneurysm (RSVA), which is a rare and mostly congenital heart disease. METHODS: From January 2014 to November 2020, 19 patients (16 males, 3 females) with RSVA were selected for TMIC and were followed up at our centre. Data were analysed from our prospectively collected database and clinical mid-term follow-up was obtained. RESULTS: Among these 19 cases, transthoracic echocardiography showed rupture of the right coronary sinus to the right atrium in 9 patients, non-coronary sinus rupture to the right atrium in 7 patients, and right coronary sinus rupture to the right ventricle in 3 patients. Most (13/19) cases were New York Heart Association (NYHA) functional class III or IV. The mean diameters of the defect from the aortic end and ruptured site were 8.8±3.0 and 6.4±2.6 mm, respectively. TMIC was attempted using ventricular septal defect (VSD)/patent ductus arteriosus (PDA) occluders 2-7 mm larger than the aortic ends of the defects. All patients were successfully treated by TMIC and achieved complete closure at discharge after a mean hospital stay length of 6.2±2.5 days. Seventeen patients were NYHA class I while 2 patients were NYHA class II. No cases of residual shunts, device embolization, infective endocarditis, or aortic regurgitation were observed during a median follow-up of 36 months (range, 16-84 months). CONCLUSIONS: In appropriately selected cases with RSVA, TMIC is an attractive alternative to surgery, with a high technical success rate and encouraging short-term and mid-term outcomes. However, long-term follow-up is needed.

Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.

BACKGROUND: The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown. METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated. RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response. CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.

Neuroprotective effect of selective hypothermic cerebral perfusion in extracorporeal cardiopulmonary resuscitation: A preclinical study.

Objective: Neurologic complications seriously affect the survival rate and quality of life in patients with extracorporeal cardiopulmonary resuscitation (ECPR) undergoing cardiac arrest. This study aimed to repurpose selective hypothermic cerebral perfusion (SHCP) as a novel approach to protect the brains of these patients. Methods: Rats were randomly allocated to Sham, ECPR, and SHCP combined ECPR (CP-ECPR) groups. In the ECPR group, circulatory resuscitation was performed at 6 minutes after asphyxial cardiac arrest by extracorporeal membrane oxygenation. The vital signs were monitored for 3 hours, and body and brain temperatures were maintained at the normal level. In the CP-ECPR group, the right carotid artery catheterization serving as cerebral perfusion was connected with the extracorporeal membrane oxygenation device to achieve selective brain cooling (26-28 °C). Serum markers of brain injury and pathomorphologic changes in the hippocampus were evaluated. Three biological replicates further received RNA sequencing in ECPR and CP-ECPR groups. Microglia activation and inflammatory cytokines in brain tissues and serum were detected. Results: SHCP rapidly reduced the brain-targeted temperature and significantly alleviated nerve injury. This was evident from the reduced brain injury serum biomarker levels, lower pathologic scores, and more surviving neurons in the hippocampus in the CP-ECPR group. Furthermore, more differentially expressed genes for inflammatory responses were clustered functionally according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. And SHCP reduced microglia activation and the release of proinflammatory mediators. Conclusions: Our preliminary data indicate that SHCP may serve as a potential therapy to attenuate brain injury via downregulation of neuroinflammation in patients with ECPR.

D-tagatose protects against oleic acid-induced acute respiratory distress syndrome in rats by activating PTEN/PI3K/AKT pathway.

Acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier, resulting in severe alveolar edema and inflammation. D-tagatose (TAG) is a low-calorie fructose isomer with diverse biological activities whose role in ARDS has never been explored. We found that TAG protects lung tissues from injury in the oleic acid-induced rat model of ARDS. Seventeen male Sprague-Dawley rats were randomly assigned to 3 groups: Sham (n = 5), ARDS (n = 6), and TAG + ARDS (n = 6). The treatment groups were injected with oleic acid to induce ARDS, and the TAG + ARDS group was given TAG 3 days before the induction. After the treatments, the effect of TAG was evaluated by blood gas analysis and observing the gross and histological structure of the lung. The results showed that TAG significantly improved the oxygenation function, reduced the respiratory acidosis and the inflammatory response. TAG also improved the vascular permeability in ARDS rats and promoted the differentiation of alveolar type II cells, maintaining the stability of the alveolar structure. This protective effect of TAG on the lung may be achieved by activating the PTEN/PI3K/AKT pathway. Thus, TAG protects against oleic acid-induced ARDS in rats, suggesting a new clinical strategy for treating the condition.

High risk of sudden death associated with a PRKAG2-related familial Wolff-Parkinson-White syndrome.

Familial appearance of Wolff-Parkinson-White (WPW) syndrome is rare and displays an autosomal dominant inheritance. Here we report a Chinese kindred of WPW syndrome whose unique clinical features consist of a high risk of sudden cardiac death due to atrial fibrillation, causing a rapid antegrade conduct over the accessory pathway. The mutation in the PRKAG2 gene was identified as responsible for the familial form of WPW syndrome.