M1 macrophage-derived exosomes inhibit cardiomyocyte proliferation through delivering miR-155.

BACKGROUND: M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. METHODS: M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. RESULTS: The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. CONCLUSION: M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages.

Rhodopseudomonas palustris shapes bacterial community, reduces Cd bioavailability in Cd contaminated flooding paddy soil, and improves rice performance.

Photosynthetic bacteria (PSB) are suitable to live and remediate cadmium (Cd) in the slightly oxygenated or anaerobic flooding paddy field. However, there is currently limited study on the inhibition of Cd accumulation in rice by PSB, and the relevant mechanisms has yet to be elucidated. In the current study, we firstly used Rhodopseudomonas palustris SC06 (a typical PSB) as research target and combined physiology, biochemistry, microbiome and metabolome to evaluate the mechanisms of remeding Cd pollution in paddy field and inhibiting Cd accumulation in rice. Microbiome analysis results revealed that intensive inoculation with R. palustris SC06 successfully survived and multiplied in flooding paddy soil, and significantly increased the relatively abundance of anaerobic bacteria including Desulfobacterota, Anaerolineaceae, Geobacteraceae, and Gemmatimonadaceae by 46.40 %, 45.00 %, 50.12 %, and 21.30 %, respectively. Simultaneously, the structure of microbial community was regulated to maintain relative stability in the rhizosphere soil of rice under Cd stress. In turn, these bacteria communities reduced bioavailable Cd and enhanced residual Cd in soil, and induced the upregulation of sugar and organic acids in the rice roots, which further inhibited Cd uptake in rice seedlings, and dramatically improved the photosynthetic efficiency in the leaves and the activities of antioxidative enzymes in the roots. Finally, Cd content of the roots, stems, leaves, and grains significantly decreased by 38.14 %, 69.10 %, 83.40 %, and 37.24 % comparing with the control, respectively. This study provides a new strategy for the remediation of Cd-contaminated flooding paddy fields and the safe production of rice.

Effects of Ulinastatin on Postoperative Renal Function in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: A Prospective Cohort Study with 10-Year Follow-Up.

INTRODUCTION: The present study aimed to explore the potential effect of ulinastatin on renal function and long-term survival in patients receiving cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This prospective cohort study was conducted at Fuwai Hospital, Beijing, China. Ulinastatin was applied after induction anesthesia. The primary outcome was the rate of new-onset postoperative acute kidney injury (AKI). Moreover, a 10-year follow-up was conducted until January 2021. RESULTS: The rate of new-onset AKI was significantly lower in the ulinastatin group than in the control group (20.00 vs. 32.40%, p = 0.009). There was no significant difference in renal replacement therapy between the two groups (0.00 vs. 2.16%, p = 0.09). The postoperative plasma neutrophil gelatinase-associated lipocalin (pNGAL) and IL-6 levels were significantly lower in the ulinastatin group compared with the control group (pNGAL: p = 0.007; IL-6: p = 0.001). A significantly lower incidence of respiratory failure in the ulinastatin group compared with the control group (0.76 vs. 5.40%, p = 0.02). The nearly 10-year follow-up (median: 9.37, 95% confidence interval: 9.17-9.57) survival rates did not differ significantly between the two groups (p = 0.076). CONCLUSIONS: Ulinastatin significantly reduced postoperative AKI and respiratory failure in patients receiving cardiac surgery with CPB. However, ulinastatin did not reduce intensive care unit and hospital stays, mortality, and long-term survival rate.

A comparison of ClearSight noninvasive cardiac output and pulmonary artery bolus thermodilution cardiac output in cardiac surgery patients.

BACKGROUND: The ClearSight system measures blood pressure non-invasively and determines cardiac output by analyzing the continuous pressure waveform. We performed a multi-center clinical study in China to test the equivalence of cardiac output measured with the ClearSight system (CSCO) and cardiac output measured with the pulmonary artery catheter bolus thermodilution (TDCO) method. METHODS: We included adult patients undergoing cardiac surgery in three Chinese hospitals and measured TDCO and CSCO simultaneously after induction of anesthesia. Hemodynamic stability was required during measurement of TDCO and CSCO. At least four TDCO determinations were performed. The corresponding CSCO was determined as the average over a 30-s period following the injection of each bolus. A data pair for the comparison included the average of three or four accepted TDCO values and the average of the matching CSCO values. Main outcomes included Bland-Altman analysis of bias and standard deviation (SD) and the percentage error (PE). RESULTS: One hundred twenty-five subjects were enrolled, and 122 TDCO and CSCO data pairs were available for analysis. Ninety-five (75.4%) data pairs were collected in hemodynamically stable conditions, mean (SD) CSCO was 4.21 (0.78) l/min, and mean TDCO was 3.90 (0.67) l/min. Bias was 0.32 (0.51) l/min, and PE was 25.2%. Analyzing all 122 data pairs resulted in a mean CSCO of 4.19 (0.82) l/min and a mean TDCO of 3.83 (0.71) l/min. Resulting bias was 0.36 (0.53) l/min, and PE was 26.4%. CONCLUSIONS: CSCO and TDCO agreed with a low systematic bias. Besides, mean PE was well below the pre-defined 30%. Hemodynamic stability only had a small impact on the analysis. We conclude that CSCO is equivalent to TDCO in cardiac surgery patients. The trial was retrospectively registered in ClinicalTrials.gov, identifier NCT03807622 ; January 17, 2019.

Effect of Clemastine Fumarate on Perioperative Hemodynamic Instability Mediated by Anaphylaxis During Cardiopulmonary Bypass Surgery.

BACKGROUND Perioperative hemodynamic instability mediated by anaphylaxis is a life-threatening complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to evaluate the effect of clemastine fumarate in this specific patient population. MATERIAL AND METHODS We enrolled 100 participants who met the inclusion criteria and randomly allocated them to the treatment group and the placebo group. Participants in the treatment group and the placebo group were treated separately with an injection of clemastine fumarate and saline, respectively. Plasma histamine concentration and blood pressure were quantified at 5 timepoints during the perioperative period, and differences between the 2 groups were assessed by repeated-measures ANOVA. The postoperative complications and in-hospital mortality also were evaluated. All participants were followed up for 7 days after cardiac surgery. RESULTS Plasma histamine concentrations increased in both groups but were statistically significantly lower in the treatment group during the perioperative period (P=0.007). Diastolic blood pressure (P=0.014) and mean arterial pressure (P=0.024) in the treatment group were significantly higher than in the placebo group during the perioperative period. The coefficients of variation for systolic (13.9±4.2% vs 17.2±4.4%, P<0.01) and diastolic (12.9±4.9% vs 15.3±5.2%, P=0.02) blood pressure were significantly lower in the treatment group compared with the placebo group. CONCLUSIONS Pretreatment with clemastine fumarate restrains the increase in histamine concentration and provides safer hemodynamics in patients undergoing cardiac surgery with CPB.

High-glucose-induced apoptosis, ROS production and pro-inflammatory response in cardiomyocytes is attenuated by metformin treatment via PP2A activation.

Metformin has been shown to ameliorate diabetic cardiomyopathy. In the present research we investigated whether metformin would reduce cardiomyocyte apoptosis that was induced by high-glucose stimulation in vitro via activation of PP2A. Primary human and rat cardiomyocytes were subject to high-glucose stimulation. Okadaic acid was used to inhibit PP2A activity. Cell viability and apoptosis was assessed using CCK-8 and by flow cytometry, respectively. Release of HMGB1, TNFα or IL-6 was analyzed by ELISA. Oxidative stress was evaluated by measuring cellular ROS and mitochondrial superoxide level. PP2A activity was evaluated by Serine/ Threonine phosphatase assay system or analyzing Y307 phosphorylation level of PP2A catalytic domain (PP2Ac) by Western blot and the association between PP2Ac and α4 by co-immunoprecipitation. Activation of the NF-κB signaling pathway was assessed by detecting Ser32 phosphorylation level of IκBα as well as nuclear entry of p65 protein by Western blot. Activation of the GSK3ß/MCL1 signaling pathway was assessed by detecting Ser9 phosphorylation level of GSK3 ß and protein level of MCL1. We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFα and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment. Metformin reduced the upregulation of PP2Ac pY307 and the PP2Ac-a4 association, which was not affected by okadaic acid treatment. Metformin pre-treatment reduced NF-κB activation in human and rat cardiomyocytes apoptosis that was elicited by high-glucose stimulation, and this effect of metformin could be blocked by okadaic acid treatment. GSK3 ß/MCL1 is not part of metformin activating PP2A induced myocardial cell death inhibition. In conclusion, metformin reduced apoptosis, ROS production and inflammatory response in primary human and rat cardiomyocytes in vitro in a PP2A dependent manner.

Effect of ulinastatin on post-operative blood loss and allogeneic transfusion in patients receiving cardiac surgery with cardiopulmonary bypass: a prospective randomized controlled study with 10-year follow-up.

BACKGROUND: Major bleeding and allogeneic transfusion leads to negative outcomes in patients receiving cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urine trypsin inhibitor, relieves systemic inflammation and improves coagulation profiles with however sparse evidence of its effects on blood loss and allogeneic transfusion in this specific population. METHODS: In this prospective randomized controlled trial, 426 consecutive patients receiving open heart surgery with CPB were randomly assigned into three groups to receive ulinastatin (group U, n = 142), tranexamic acid (group T, n = 143) or normal saline (group C, n = 141). The primary outcome was the total volume of post-operative bleeding and the secondary outcome included the volume and exposure of allogeneic transfusion, the incidence of stroke, post-operative myocardial infarction, renal failure, respiratory failure and all-cause mortality. A ten-year follow-up was carried on to evaluate long-term safety. RESULTS: Compared with placebo, ulinastatin significantly reduced the volume of post-operative blood loss within 24 h (688.39 ± 393.55 ml vs 854.33 ± 434.03 ml MD - 165.95 ml, 95%CI - 262.88 ml to - 69.01 ml, p < 0.001) and the volume of allogeneic erythrocyte transfusion (2.57 ± 3.15 unit vs 3.73 ± 4.21 unit, MD-1.16 unit, 95%CI - 2.06 units to - 0.26 units, p = 0.002). The bleeding and transfusion outcomes were comparable between the ulinastatin group and the tranexamic acid group. In-hospital outcomes and 10-year follow-up showed no statistical difference in mortality and major morbidity among groups. CONCLUSIONS: Ulinastatin reduced post-operative blood loss and allogeneic erythrocyte transfusion in heart surgery with CPB. The mortality and major morbidity was comparable among the groups shown by the 10-year follow-up. TRIAL REGISTRATION: The trial was retrospectively registered on February 2, 2010. TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov Identifier: NCT01060189.

Ulinastatin reduces postoperative bleeding and red blood cell transfusion in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05. RESULTS: Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003). CONCLUSION: This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.

Efficacy and Safety of Tranexamic Acid in Pediatric Patients Undergoing Cardiac Surgery: A Single-Center Experience.

Aims: This study evaluated the efficacy and safety of tranexamic acid (TXA) undergoing cardiac surgery. Methods: Using a retrospective cohort study design, 2,026 consecutive pediatric patients who underwent surgical repair of atrial or ventricular septal defect or complete repair of Tetralogy of Fallot were included, and divided into a control group and a TXA group. Results: Compared with that in the control group, there were statistically significant reduction of both the 12-h and total postoperative blood loss in the TXA group [6.573 ± 0.144 vs. 5.499 ± 0.133 ml kg-1, mean difference (MD) 1.074 ml kg-1, p < 0.001; 12.183 ± 0.298 vs. 9.973 ± 0.276 ml kg-1, MD, 2.210 ml kg-1, p < 0.001]. There was a statistically significant reduction of the MD of 12-h postoperative blood loss due to TXA in patients aged < 1 year compared with that in patients aged ≥1 year (MD, 1.544 vs. 0.681 ml kg-1, P = 0.007). There were statistically significant reduction of the MD of both the 12-h and total postoperative blood loss due to TXA in patients weighing < 10 kg compared with that in patients weighing ≥10 kg (MD, 1.542 vs. 0.456 ml kg-1, P < 0.001, and MD, 2.195 vs. 0.929 ml kg-1, P = 0.036, respectively). There was a statistically significant reduction of the MD of total postoperative blood loss due to TXA in cyanotic patients compared with that in acyanotic patients (MD, 3.381 vs. 1.038 ml kg-1, P = 0.002). There was no significant difference in the postoperative volume or exposure of allogeneic transfusion, in-hospital morbidity or mortality between the groups. Conclusions: TXA took effects in reduction of postoperative blood loss but not the allogeneic transfusion requirement in pediatric patients undergoing cardiac surgery, particularly in infants weighing < 10 kg and cyanotic children. Moreover, the study suggested the use of TXA was safe in pediatric cardiac surgery.

Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway.

OBJECTIVE: To analyze the effects of miR-455-3p-1 and its possible mechanisms in pulmonary arterial hypertension (PAH). METHODS: A microarray assay was used to examine the expressed genes between normal and PAH. The expressed genes in PAH was assessed by qRT-PCR. The targeted interaction between miRNAs and FGF7 was confirmed using a dual luciferase reporter assay. A CCK-8 assay and cell count were used to analyze the pulmonary artery smooth muscle cells (PASMCs) activity and proliferation level, respectively. Apoptotic PASMCs were detected by flow cytometry. In addition, the mRNA and protein expression levels of RAS/ERK signaling pathway were determined by qRT-PCR and a Western blot assay, respectively. A PAH rat model was used to identify the effects of miR-455-3p-1 in vivo. RESULTS: FGF7 was upregulated in PAH. MiR-455-3p-1 was downregulated in PAH. MiR-455-3p-1 targeted FGF7. MiR-455-3p-1 decreased the expression of FGF7. Moreover, the effect of FGF7 on PASMCs was suppressed by miR-455-3p-1. MiR-455-3p-1 upregulation was associated with reduced mRNA and protein levels of core RAS/ERK signal genes, suggesting the inhibition of the RAS/ERK pathway. Furthermore, miR-455-3p-1 upregulation improved the RVSP, mPAP, ratio of RV/LV + S, CO and RV function of PAH rat model in vivo. CONCLUSION: Our findings illustrate a role for miR-455-3p-1 in modulating FGF7-RAS/ERK signaling and suggest that an agomir of miR-455-3p-1 could inhibit the proliferation of PASMCs and mitigate PAH in vivo.

Long non-coding RNA CASC2 suppresses pulmonary artery smooth muscle cell proliferation and phenotypic switch in hypoxia-induced pulmonary hypertension.

BACKGROUND: In this study, we aimed to investigate whether and how lncRNA CASC2 was involved in hypoxia-induced pulmonary hypertension (PH)-related vascular remodeling. METHODS: The expression of lncRNAs or mRNAs was detected by qRT-PCR, and western blot analysis or immunochemistry was employed for detecting the protein expression. Cell number assay and EdU (5-ethynyl-2'-deoxyuridine) staining were performed to assess cell proliferation. Besides, flow cytometry and wound healing assay were employed for assessments of cell apoptosis and cell migration, respectively. Rat model of hypoxic PH was established and the hemodynamic measurements were performed. Hematoxylin and eosin (HE) and Masson's trichrome staining were carried out for pulmonary artery morphometric analysis. RESULTS: The expression of lncRNA CASC2 was decreased in hypoxia-induced rat pulmonary arterial tissues and pulmonary artery smooth muscle cells (PASMCs). Up-regulation of lncRNA CASC2 inhibited cell proliferation, migration yet enhanced apoptosis in vitro and in vivo in hypoxia-induced PH. Western blot analysis and immunochemistry showed that up-regulation of lncRNA CASC2 greatly decreased the expression of phenotype switch-related marker α-SMA in hypoxia-induced PH. Furthermore, it was indicated by the pulmonary artery morphometric analysis that lncRNA CASC2 suppressed vascular remodeling of hypoxia-induced rat pulmonary arterial tissues. CONCLUSION: LncRNA CASC2 inhibited cell proliferation, migration and phenotypic switch of PASMCs to inhibit the vascular remodeling in hypoxia-induced PH.

Effects of tranexamic acid on short-term and long-term outcomes of on-pump coronary artery bypass grafting: Randomized trial and 7-year follow-up.

AIMS: Safety evaluations of tranexamic acid (TXA) remain sparse, especially with respect to its impact on long-term outcomes in patients undergoing on-pump coronary artery bypass grafting (CABG). We hypothesized that the effects of TXA on perioperative bleeding and allogeneic transfusion and its impact on long-term clinical outcomes of patients receiving on-pump CABG are superior to those in the control group. METHODS: In this prospective, randomized, placebo-controlled trial, 210 patients undergoing primary and isolated on-pump CABG were randomly assigned to receive TXA or a corresponding volume of saline solution. Randomly assigned patients were followed up at 1, 3, 5, and 7 years after hospital discharge. Finally, 163 patients fulfilled the 7-year follow-up. The primary outcome was allogeneic red blood cell (RBC) transfusion. Long-term mortality and morbidity were also evaluated. RESULTS: Compared with placebo, TXA reduced the allogeneic RBC requirement in terms of the volume transfused (4.20 ± 4.06 vs 6.25 ± 4.86 units; P < 0.01), ratio exposed (52.0% vs 71.6%; P < 0.01), and blood loss volume (879.0 ± 392.5 vs 1154.0 ± 582.8 mL; P < 0.01). Except for myocardial infarction, there were no significant differences in mortality or morbidity between the two groups during the 7-year follow-up. The TXA group had a lower rate of myocardial infarction than did the placebo group (0.0% vs 4.9% at 84 months; P = 0.03). CONCLUSIONS: Tranexamic acid significantly decreased postoperative bleeding and allogeneic transfusion in patients undergoing on-pump CABG. The 7-year follow-up suggested that the use of TXA was safe and might play a potential role in the prevention of long-term myocardial infarction.

Downregulation of Na+/Ca2+ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats.

BACKGROUND:: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+/Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. METHODS:: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. RESULTS:: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% ± 4.54% in the SevoPoC group [P = 0.0006], and 22.34% ± 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% ± 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 ± 0.09 in the I/RI group vs. 0.32 ± 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 ± 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). CONCLUSION:: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.

Effects of Ulinastatin on In Vitro Storage Lesions of Human Red Blood Cells.

BACKGROUND: The study aimed to investigate the influence of in vitro storage on erythrocyte complement receptor one (E-CR1), cell shrinkage and eryptosis of human red blood cells (RBCs), and to assess the possible effects of ulinastatin (UTI) on them. METHODS: After collection, RBCs were treated with saline (control group) and different concentrations of UTI (5,000 U/mL, 10,000 U/mL, and 50,000 U/mL in Group C1, Group C2, and Group C3, respectively). E-CR1, cell size, and phosphatidylserine (PS) exposure and intracellular Ca2+ concentration were analyzed by flow cytometer every 7 days up to Day 35. RESULTS: E-CR1 level and cell size of all groups decreased during storage. In the control group, E-CR1 began to decrease on Day 28 and cells shrank on Day 21. The E-CR1 level of Group C2 was significantly higher than that of the control group beginning on Day 21. The cells of Group C1 and Group C2 began to shrink remarkably on Day 21, and those of Group C3 on Day 35. PS-exposure levels of 4 groups started to increase on Day 7 (p < 0.05), while from Day 14 to 35 those of Group C3 were significantly lower than the control group (p < 0.05). The intracellular Ca2+ levels of the control group started to increase significantly on Day 7, one week earlier than the experimental groups. From Day 21 to 35, the intracellular Ca2+ levels of Group C2 and C3 were significantly lower than those of the control group (p < 0.05). CONCLUSIONS: RBCs underwent E-CR1 loss, cell shrinkage, and eryptosis during in vitro storage, which could be attenuated by UTI.

Age and Surgical Complexity impact on Renoprotection by Remote Ischemic Preconditioning during Adult Cardiac Surgery: A Meta analysis.

We aimed to conduct an up-to-date meta-analysis to comprehensively assess the renoprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing adult cardiac surgery. 21 randomized controlled trials (RCTs) with a total of 6302 patients were selected and identified. Compared with controls, RIPC significantly reduced the incidence of acute kidney injury (AKI) [odds ratio (OR) = 0.79; P = 0.02; I2 = 38%], and in particular, AKI stage I (OR = 0.65; P = 0.01; I2 = 55%). RIPC significantly shortened mechanical ventilation (MV) duration [weighted mean difference (WMD) = -0.79 hours; P = 0.002; I2 = 53%), and reduced intensive care unit (ICU) stay (WMD = -0.23 days; P = 0.07; I2 = 96%). Univariate meta-regression analyses showed that the major sources of heterogeneity for AKI stage I were age (coefficient = 0.06; P = 0.01; adjusted R2 = 0.86) and proportion of complex surgery (coefficient = 0.02; P = 0.03; adjusted R2 = 0.81). Subsequent multivariate regression and subgroup analyses also confirmed these results. The present meta-analysis suggests that RIPC reduces the incidence of AKI in adults undergoing cardiac surgery and this benefit was more pronounced in younger patients undergoing non-complex cardiac surgery. RIPC may also shorten MV duration and ICU stay. Future RCTs tailored for those most likely to benefit from RIPC warrants further investigation.

Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: A randomized controlled trial.

BACKGROUND: Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery. METHODS: This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality. RESULTS: Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% [30/142] in the DEX group vs 33.6% [48/143] in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% [120/142] in the DEX group vs 69.9% [100/143] in the CTRL group, p = 0.003). CONCLUSIONS: Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267538.

Simultaneous hybrid coronary revascularization versus off-pump coronary artery bypass grafting for diabetic patients with multivessel coronary artery disease / 中国胸心血管外科临床杂志

@#Objective    To compare the in-hospital and midterm outcomes after simultaneous hybrid coronary revascularization (HCR) with off-pump coronary artery bypass grafting (OPCAB) in diabetic patients with multivessel coronary artery disease. Methods    One hundred thirty-two diabetic patients with multivessel coronary artery disease underwent one-stop HCR at Fuwai Hospital from January 2010 to January 2015. These patients were 1∶2 matched with those who underwent OPCAB using propensity score matching. Results    Simultaneous HCR had less chest tube drainage (618 (420, 811) ml vs. 969 (711, 1 213)ml, P<0.001), lower transfusion rate (19.7% vs. 34.1%, P=0.026), shorter mechanical ventilation time (11.6 (8.2, 14.8) h vs. 16.0 (12.1, 18.7) h, P<0.001), and shorter stay in intensive care unit (21.5 (18.8, 42.0)   h vs. 44.6 (23.7, 70.1) h, P<0.001) than OPCAB. During over median 40 months follow-up, simultaneous HCR offered similar major adverse cardiac or cerebrovascular events (MACCE) rate (6.8% vs 9.0%, P=0.826), but lower stroke rate (0%vs 3.0%, P=0.029), compared with OPCAB. Conclusion    For selected patients with diabetes, simultaneous HCR provides a safe and effective revascularization alternative. It decreases perioperative invasiveness and incurred similar and favorable midterm outcomes with OPCAB.

Renoprotection by remote ischemic conditioning during elective coronary revascularization: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Remote ischemic conditioning (RIC) has been recognized an emerging non-invasive approach for preventing acute kidney injury (AKI) in patients undergoing either elective coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). On the other hand, accumulating evidence has indicated the involving role of pre-CABG contrast usage for coronary angiography in post-surgery AKI risk. Along with the shortening time delay of CABG after coronary angiography, and the prevalent hybrid coronary revascularization (HCR), the AKI prevention by RIC has faced challenges following coronary revascuralization. METHODS: Randomized controlled trials (RCTs) were searched from Pubmed, EMBase, and Cochrane library (until May 2016). The primary outcome was postoperative AKI. The second outcomes were included the requirement for renal replacement therapy (RRT), and in-hospital or 30-day mortality. RESULTS: Twenty eligible RCTs (CABG, 3357 patients; PCI, 1501 patients) were selected. RIC significantly halved the incidence of AKI following PCI when compared with controls [n=1501; odds ratio (OR)=0.51; 95% CI, 0.32 to 0.82; P=0.006; I(2)=29.6%]. However, RIC did not affect the incidence of AKI following CABG (n=1850; OR=0.94; 95% CI, 0.73 to 1.19; P=0.586; I(2)=12.4%). The requirement for RRT and in-hospital mortality was not affected by RIC in CABG (n=2049, OR=1.04, P=0.87; n=1920, OR=0.89, P=0.7; respectively). CONCLUSIONS: Our meta-analysis suggests that RIC for preventing AKI following CABG has faced with challenges in terms of AKI, the requirement for RRT, and mortality. However, RIC shows a renoprotective benefit for PCI. Hence, our findings may infer the preserved renal effects of RIC in CABG with preconditioning before the coronary angiography, or in HCR.

One-stop hybrid coronary revascularization versus off-pump coronary artery bypass in patients with diabetes mellitus.

OBJECTIVES: To compare in-hospital and midterm outcomes after one-stop hybrid coronary revascularization (HCR) and off-pump coronary artery bypass (OPCAB) in patients with diabetes mellitus (DM). METHODS: The series included 120 patients with DM who underwent one-stop HCR at Fuwai Hospital between June 2007 and September 2014. These patients were 1:2 matched with 240 patients who underwent OPCAB using propensity score matching. The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE) over midterm follow-up, and secondary endpoints were in-hospital outcomes. Accounting for matched-pairs design, the survival analysis was evaluated with a marginal Cox model, and the continuous and dichotomous variables of in-hospital outcomes were compared with the Wilcoxon signed-rank test and a logistic regression model using generalized estimating equations, respectively. RESULTS: Compared with OPCAB, one-stop HCR was associated with less chest tube drainage (median, 748 mL [interquartile range (IQR), 540-1080 mL] vs 990 mL [IQR, 730-1250 mL]; P < .001), a lower packed red blood cell transfusion rate (18.3% vs 29.6%; P = .032), shorter mechanical ventilation time (median, 13.7 hours [IQR, 10.3-16.9 hours] vs 16.8 hours [IQR, 13.0-19.6 hours]; P < .001), and shorter stay in intensive care unit (median 21.7 hours [IQR, 19.0-44.3 hours] vs 46.7 hours [IQR, 24.3-72.7 hours]; P < .001). Over 30 months of follow-up, one-stop HCR and OPCAB had a similar rate of MACCE (7.4% vs 8.0% at 3 years; hazard ratio, 0.807; 95% confidence limit, 0.352-1.849; P = .612), but one-stop HCR had a lower stroke rate (0% vs 3.6% at 3 years; P = .046). CONCLUSIONS: For selected patients with DM, one-stop HCR provided safe and reproducible revascularization, with less perioperative invasiveness and similar and favorable midterm outcomes compared with OPCAB.