Aldehyde dehydrogenase 2 serves as a key cardiometabolic adaptation regulator in response to plateau hypoxia in mice.

High-altitude heart disease (HAHD) is a complex pathophysiological condition related to systemic hypobaric hypoxia in response to transitioning to high altitude. Hypoxia can cause myocardial metabolic dysregulation, leading to an increased risk of heart failure and sudden cardiac death. Aldehyde dehydrogenase 2 (ALDH2) could regulate myocardial energy metabolism and plays a protective role in various cardiovascular diseases. This study aims to determine the effects of plateau hypoxia (PH) on cardiac metabolism and function, investigate the associated role of ALDH2, and explore potential therapeutic targets. We discovered that PH significantly reduced survival rate and cardiac function. These effects were exacerbated by ALDH2 deficiency. PH also caused a shift in the myocardial fuel source from fatty acids to glucose; ALDH2 deficiency impaired this adaptive metabolic shift. Untargeted/targeted metabolomics and transmission electron microscopy revealed that ALDH2 deficiency promoted myocardial fatty-acid deposition, leading to enhanced fatty-acid transport, lipotoxicity and mitochondrial dysfunction. Furthermore, results showed that ALDH2 attenuated PH-induced impairment of adaptive metabolic programs through 4-HNE/CPT1 signaling, and the CPT1 inhibitor etomoxir significantly ameliorated ALDH2 deficiency-induced cardiac impairment and improved survival in PH mice. Together, our data reveal ALDH2 acts as a key cardiometabolic adaptation regulator in response to PH. CPT1 inhibitor, etomoxir, may attenuate ALDH2 deficiency-induced effects and improved cardiac function in response to PH.

Using healthcare failure mode and effect analysis as a method of vaginal birth after caesarean section management.

AIMS AND OBJECTIVES: This research was conducted to explore the effectiveness of employing the healthcare failure mode and effect analysis method in the management of trial of labour after caesarean, with the aims of increasing vaginal birth after caesarean section rate and reducing potential risks that might cause severe complications. BACKGROUND: Previously high caesarean section rate in China and the "two children" policy leads to the situation where multiparas are faced with the choice of another caesarean or trial of labour after caesarean. Despite evidences showing the benefits of vaginal birth after caesarean, obstetricians and midwives in China tend to be conservative due to limited experience and insufficient clinical routines. Thus, its management needs further optimisation in order to make the practice safe and sound. DESIGN: A prospective quality improvement programme using the healthcare failure mode and effect analysis. METHODS: With the structured methodology of healthcare failure mode and effect analysis, we determined core processes of antepartum and intrapartum management, conducted risk priority numbers and devised remedial protocols for failure modes with high risks. The programme was then implemented as a clinical routine under the agreement of the institutional review board and vaginal birth after caesarean success rates were compared before and after the quality improvement programme, both descriptively and statistically. Standards for Quality Improvement Reporting Excellence 2.0 checklist was chosen on reporting the study process. RESULTS: Seventy failure modes in seven core processes were identified in the management process, with 14 redressed for actions. The 1-year follow-up trial of labour after caesarean and vaginal birth after caesarean rate was increased compared with the previous 3 years, with a vaginal birth after caesarean rate of 86.36%, whereas the incidence of uterine rupture was not compromised. CONCLUSIONS: The application of healthcare failure mode and effect analysis can not only promote trial of labour after caesarean and vaginal birth after caesarean rate, but also maintaining a low risk of uterine rupture. RELEVANCE TO CLINICAL PRACTICE: This modified vaginal birth after caesarean management protocol has been shown effective in increasing its successful rate, which can be continued for further comparison of severe complications to the previous practice.

Nanoparticle Delivery Systems for DNA/RNA and their Potential Applications in Nanomedicine.

The rapid development of nanotechnology has a great influence on the fields of biology, physiology, and medicine. Over recent years, nanoparticles have been widely presented as nanocarriers to help the delivery of gene, drugs, and other therapeutic agents with cellular targeting ability. Advances in the understanding of gene delivery and RNA interference (RNAi)-based therapy have brought increasing attention to understanding and tackling complex genetically related diseases, such as cancer, cardiovascular and pulmonary diseases, autoimmune diseases and infections. The combination of nanocarriers and DNA/RNA delivery may potentially improve their safety and therapeutic efficacy. However, there still exist many challenges before this approach can be practiced in the clinic. In this review, we provide a comprehensive summary on the types of nanoparticle systems used as nanocarriers, highlight the current use of nanocarriers in recombinant DNA and RNAi molecules delivery, and the current landscape of gene-based nanomedicine-ranging from diagnosis to therapeutics. Finally, we briefly discuss the biosafety concerns and limitations in the preclinical and clinical development of nanoparticle gene systems.

LncRNA-LINC00472 contributes to the pathogenesis of atrial fibrillation (Af) by reducing expression of JP2 and RyR2 via miR-24.

BACKGROUND: Dysregulated methylation of the promoter of lncRNA LINC00472 reduces the expression of LINC00472 and subsequently up-regulates the expression of its competing endogenous RNA miR-24. In addition, JP2 can stabilize the expression of RyR2, whereas the deregulation of RyR2 expression may contribute to the pathogenesis of atrial fibrillation (AF). In this study, we aimed to study the role of LINC00472 in the pathogenesis of AF. METHODS: 125 AF patients and 168 healthy controls were enrolled to compare their expression of miR-24, LINC00472, JP2 and RyR2. A dual-luciferase reporter gene assay accompanied by real-time PCR, Western blot and IHC assay was subsequently conducted to evaluate the regulatory relationship among miR-24, LINC00472, JP2 and RyR2 in HCM and H9C2 cells. RESULTS: AF patients were associated with an increased level of miR-24 expression and reduced level of LINC00472 expression. Also, the level of DNA methylation in LINC00472 was increased in AF patients. MiR-24 could negatively regulate the expression of LINC00472 and JP2 by directly binding to them. CONCLUSIONS: LINC00472 could regulate the progression of AF via modulating the LINC00472/miR-24/JP2/RyR2 signaling pathway.

Benefits may not outweigh risks of low molecular weight heparin (LMWH) in early postoperative thromboprophylaxis following minimally invasive cardiac surgery: a propensity score-matched analysis.

BACKGROUND: Whether the benefits of early prophylactic anticoagulation by low molecular weight heparin (LMWH) would outweigh its possible harms in patients after minimally invasive cardiac surgery (MICS) remains contentious. The aims of this study were to define the incidence of venous thromboembolism (VTE) and to assess whether early prophylactic anticoagulation by LMWH postoperatively was indeed effective in reducing VTE without increasing risk of complications after MICS. METHODS: This investigation was a single-center, retrospective, propensity score-matched analysis study. A total of 473 patients underwent MICS, of whom 257 received prophylactic anticoagulation with LMWH (LMWH group) in the early postoperative period and 216 were not treated with LMWH (Control group). The main outcome measurements included the incidence of embolism events and major bleeding events, the volume of erythrocyte transfusion, the volume of drainage and the duration of drainage after MICS. In addition, the incidence of poor wound healing, the mechanical ventilation time, ICU stay time and postoperative hospitalization time were also documented. RESULTS: There were fewer embolic events (P=1.000) and a higher rate of major bleeding events (P=0.008) in the LMWH group than the Control group, and their magnitude and significance were maintained in the propensity matched analysis. In the matched cohorts, there was no significant difference in the total volume of red blood cell transfusion (P=0.552), assisted mechanical ventilation time (P=0.542), and the ICU stay time (P=0.166) between the two groups; while the volume of drainage (P<0.001) and the duration of drainage (P<0.001) in the LMWH group were significantly more than the Control group, and the incidence of poor wound healing (P=0.009) and the postoperative hospitalization time (P<0.001) were significantly increased in the LMWH group. CONCLUSIONS: Early prophylactic anticoagulation with LMWH could not reduce the incidence of embolism events after MICS. Instead, it might increase postoperative major bleeding events and prolong drainage tube indwelling time and the length of hospital stay.

Short-term outcomes of minimally invasive mitral valve repair: a propensity-matched comparison.

OBJECTIVES: We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary function and haemodynamics, as well as its short-term efficacy. METHODS: From March 2012 to July 2015, 78 cases of minimally invasive mitral valve repair and 89 cases of conventional mitral valve repair were included in this study, with 67 well-matched pairs of patients identified by a propensity score matching, who were divided into the conventional sternotomy group and the right minithoracotomy group (the RT group). RESULTS: The in-hospital mortality was similar between the 2 groups (3.0% vs 1.5%, P = 1.000). Both cross-clamp time and bypass time were higher in the RT group (P < 0.001), whereas drainage amount, blood transfusion and length of intensive care unit stay were higher in the conventional sternotomy group (P < 0.001). There was not much discrepancy in pulmonary function between the 2 groups, except that partial pressure of O2 in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) in the RT group was significantly lower than that in the conventional sternotomy group 0, 4 and 8 h after surgery (P < 0.05), whereas the extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI) and alveolar-arterial PO2 difference (PA-aO2) of the RT group was higher (P < 0.05). We found no disparity in haemodynamics (P > 0.05), incidence of complications (P > 0.05) and short-term recurrence between the 2 groups (P = 0.7697). CONCLUSIONS: When compared with the median sternotomy approach, the RT approach shows comparable results in short-term efficacy and safety. On relatively increasing cardiopulmonary bypass time and operation time, the RT approach shortens the patient's intensive care unit stay and reduces the need for blood transfusion. Pulmonary function may be affected shortly post-surgery in the RT approach, with insignificant difference in haemodynamics.

Entry-Level Forward Surgical Team Training in 5th Grade Students of Second Military Medical University of the Chinese People's Liberation Army.

BACKGROUND: Forward surgical team (FST) is a highly mobile team for surgical missions in battlefield. FST training has been well held in many western countries. However, such training in Chinese army is far from satisfaction. METHODS AND RESULTS: Relying on Second Military Medical University and its affiliated hospitals, we are launching an entry-level training program for 5th grade students, in order to improve their understandings on basic concepts of FST, as well as their abilities to complete surgical missions on battlefield. CONCLUSIONS: In this article, we are going to introduce our training facilities as well as our training methods in our training program.

Continuous administration of recombinant human B-type natriuretic peptide can improve heart and renal function in patients after cardiopulmonary bypass surgery.

BACKGROUND: Any cardiac surgery under cardiopulmonary bypass (CPB) will induce ischemia-reperfusion injury and systematic inflammatory response, which may lead to exacerbation. Conventional therapy strategy is to use inotropes, diuretics and vasodilator drugs, yet, the therapeutic effects of which need to be improved. Recombinant human B-type natriuretic peptide (rhBNP) has been shown to be efficacious in the treatment of acute decompensated heart failure and acute myocardial infarction. However, the effects of rhBNP on patients carried out CPB surgery is unknown. METHODS: We retrospect 357 patients carried out CPB surgery between Jan 1st 2014 and Dec 31st 2015 of our department. And according the use of rhBNP, these patients were divided into two groups: rhBNP group and control group. Patients in rhBNP group were received continuous intravenous rhBNP (0.0075-0.01 µg/kg/min) in 6 hours after CPB surgery, for a period of 72 h. Hemodynamic parameters were measured immediately after CPB surgery, and then at 2, 4, 8, 12 and 24 h after surgery. Blood samples were obtained immediately after surgery and thereafter once a day at 6:00 AM within the first 3 days after surgery. The daily urine volume as well as the time of tracheal intubation, ICU stay and chest drainage were also recorded. RESULTS: The baseline characteristics and heart functions were well balanced between two groups, and no patient died in the surgery. It showed significant differences in time-dependent changes in both groups of MAP (P<0.0001, within groups), MPAP (P<0.0001, within groups), PAWP (P<0.0001, within groups), CI (P<0.0001, within groups), SVRI (P<0.0001, within groups), serum BNP (P<0.0001, within groups), CK-MB (P<0.0001, within groups), troponin (P<0.0001, within groups) and creatinine (P<0.0001, within groups). It also showed significant differences in time-dependent changes between the two groups of MAP (P=0.04, between groups), PAWP (P=0.04, between groups), serum troponin (P<0.0001, between groups), serum creatinine (P<0.0001, between groups) and urine volume (P<0.0001, between groups). Interestingly, our results showed that patients in rhBNP group tended to wean off the respirator half a day later than those in control group (P=0.05), while no significant difference showed in both the length of chest drainage time and intensive care unit stay between the two groups. CONCLUSIONS: The administration of rhBNP can improve heart and renal function in patients underwent CPB surgery as well as accelerating the recovery from myocardial injury. But the prognosis of the patients who were administrated rhBNP did not improve in our study.