Macrophage-mediated mechanisms of lung injury in the sensitization reaction to Echinococcus granulosus.

Objective: In this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated. Methods: Twenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels. Results: Mice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05). Conclusion: Our results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

The regulatory role of differential microRNA expressions on cellular inflammatory factors IL-6 and IL-10 in Echinococcus granulosus-induced anaphylaxis.

OBJECTIVE: To determine the pathogenesis and molecular targets of anaphylaxis caused by hydatid cyst fluid leakage. METHODS: First, Balb/c mice were infected with Echinococcus granulosus, and then the anaphylaxis model was developed. The mice were separated into: anaphylaxis caused by the cystic echinococcosis group (ANPC), the cystic echinococcosis without anaphylaxis group (CE group), and the normal control group (CTRL). Following this, the spleen tissue was collected for microRNA (miRNA) sequencing. Using bioinformatics analysis, differentially expressed miRNAs (DEMs) were identified. Then, through the use of protein-protein interaction (PPI) networks, the key target genes for miRNA regulation associated with echinococcosis-induced anaphylaxis were identified. RESULTS: ANPC and CE groups have 29 and 39 DEMs compared to the CTRL group, respectively. Based on these 25 DEMs, interactions between miRNA and mRNA were screened, and 174 potential target genes were identified. We performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on these 174 target genes, and the results revealed that the three pathways with the highest enrichment were the PI3K-Akt signaling pathway, FoxO signaling pathway, and Focal adhesion. The interaction analysis of PPI and miRNA-hub gene networks revealed that interleukin 6 (IL-6) was regulated by miR-146a-5p and miR-149-5p, while IL-10 was regulated by miR-29b-3p and miR-29c-3. Using reverse transcription polymerase chain reaction, we found that the miRNAs regulating IL-6 and IL-10 were significantly upregulated in the ANPC group, and there are three pathways involved in that process: Pathways of PI3K-Akt signaling, FoxO signaling, and Focal adhesion. IL-6 and IL-10 play an important role in cellular pyroptosis and apoptosis. Therefore, the aforementioned results provide significant reference value for elucidating the mechanism of cellular pyroptosis and apoptosis in echinococcosis-induced anaphylaxis, and for formulating tissue and organ protection strategies for patients with cystic echinococcosis when anaphylaxis is triggered by hydatid cyst rupture.

Understory vegetation diversity, soil properties and microbial community response to different thinning intensities in Cryptomeria japonica var. sinensis plantations.

Introduction: Soil microorganisms are the key factors in elucidating the effects of thinning on tree growth performance, but the effects of vegetation and soil on the species composition and function of soil microorganisms after thinning are still not well elaborated. Methods: The effects of thinning on understory vegetation diversity, soil physicochemical properties and soil microbial community composition were investigated in a thinning trial plantation of Cryptomeria japonica var. sinensis, including four thinning intensities (control: 0%, LIT: 20%, MIT: 30% and HIT: 40%), and the relationships of the microbial community structure with the understory vegetation diversity and soil properties were assessed. Results: The results showed that thinning had a greater effect on the diversity of the shrub layer than the herb layer. The soil bulk density and the contents of soil organic matter, total potassium and nitrogen increased with increasing thinning intensities. The Shannon and Chao indices of soil bacteria and fungi were significantly lower in the LIT, MIT and HIT treatments than in the control. Thinning can significantly increase the abundance of Proteobacteria and Actinobacteria, and higher thinning intensities led to a higher relative abundance of Ascomycota and a lower relative abundance of Basidiomycota, Rozellomycota, and Mortierellomycota. Redundancy analysis indicated that soil physicochemical properties rather than understory vegetation diversity were the main drivers of microbial communities, and fungi were more sensitive to soil properties than bacteria. Functional prediction showed that thinning significantly reduced the potential risk of human diseases and plant pathogens, and the nitrogen fixation capacity of bacteria was the highest in the HIT treatment. Thinning significantly increased the relative abundance of cellulolysis and soil saprotrophs in bacteria and fungi. Conclusion: The findings provide important insights into the effects of thinning on C. japonica var. sinensis plantation ecosystems, which is essential for developing thinning strategies to promote their ecological and economic benefits.

Early postoperative organ dysfunction is highly associated with the mortality risk of patients with type A aortic dissection.

OBJECTIVES: This study assessed the impact of early postoperative organ dysfunction (EPOD) on in-hospital mortality of patients with type A aortic dissection (TAAD) after surgery. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest from January 2020 to December 2021 were included. The Sequential Organ Failure Assessment (SOFA) score was calculated for 3 days postoperatively to stratify the severity of organ dysfunction. Patients with the SOFA of 0-4, 5-8 or >8 were defined as mild, moderate or severe EPOD. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Kaplan-Meier curves were used to compare survival probability. The area under the receiver operating characteristic curve and calibration plots were used to evaluate the predictive power and overall performance of SOFA. RESULTS: Of the 368 patients, 5 patients (3%) with moderate EPOD and 33 patients (23%) with severe EPOD died. No patient died with mild EPOD. The areas under the receiver operating characteristic curve of SOFA for predicting mortality and the composite outcome were 0.85 (0.81-0.88) and 0.81 (0.77-0.85) on postoperative day 1. Each point of postoperative day 1 SOFA score corresponded to an odds ratio of 1.65 (1.42-1.92) for mortality. Of the 6 components of the SOFA system, only coagulation (2.34 [1.32-4.13]), cardiovascular (1.47 [1.04-2.08]), central nervous system (1.96 [1.36-2.82]) and renal (1.67 [1.04-2.70]) functions were associated with the higher risk of mortality. CONCLUSIONS: EPOD stratified by the SOFA score was associated with a higher risk of death and predicted the clinical outcomes of patients with TAAD with good accuracy.

Mesobacterium pallidum gen. nov., sp. nov., Heliomarina baculiformis gen. nov., sp. nov. and Oricola indica sp. nov., three novel Alphaproteobacteria members isolated from deep-sea water in the southwest Indian ridge.

Three Gram-staining-negative, aerobic and rod-shaped strains, designated as T40-1T, T40-3T and JL-62T, were isolated from the deep-sea water in the southwest Indian ridge. For strain T40-1T, growth occurred at 15-37 °C (optimum, 28 °C), pH 6.0-9.0 (optimum, pH 7.5) and in the presence of 0.5-5.0 % NaCl (w/v; optimum, 2.0 %). Strain T40-3T could grow at 15-40 °C (optimum, 28 °C), with 0.5-11.0 % NaCl (optimum, 2.0 %, w/v) at pH 6.0-9.5 (optimum, 8.0). The temperature, pH and salinity ranges for growth of strain JL-62T were 15-40 °C (optimum, 30 °C), pH 5.5-9.0 (optimum, pH 7.5-8.0) and 0.5-9.0 % NaCl (w/v; optimum, 4.0 %). Ubiquinone-10 was the sole ubiquinone in all strains, the major fatty acids (>20 %) were summed feature 8 (C18 : 1 ω7c / C18 : 1 ω6c). The major polar lipids of strains T40-1T and T40-3T were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. Strain JL-62T contained phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and sulfoquinovosyldiacylglycerol as major polar lipids. Phylogenetic trees based on 16S rRNA gene and core-genomic sequences revealed affiliation of strains T40-1Tand T40-3T to the family Roseobacteraceae and formed two independent clades from other Roseobacteraceae genera, and those two strains had average nucleotide identities of 62.0-72.0 % to their phylogenetically related species which fell into to the genus boundary range, indicating that they represent two novel genera. While strain JL-62T represents a novel species in the genus Oricola belonging to the family Phyllobacteriaceae, which was supported by overall genomic relatedness index calculations. The DNA G+C contents of strains T40-1T, T40-3T and JL-62T were 66.5, 60.1 and 62.1 mol %, respectively. Based on the polyphasic taxonomic data, strains T40-1T (=MCCC M24557T=KCTC 82975T) and T40-3T (=MCCC 1K05135T=KCTC 82976T) are classified as representing two novel genera belonging to the family Roseobacteraceae with the names Mesobacterium pallidum gen. nov., sp. nov. and Heliomarina baculiformis gen. nov., sp. nov. are proposed, and strain JL-62T (=MCCC M24579T=KCTC 82974T) is proposed to represent a novel species within the genus Oricola with the name Oricola indica sp. nov. is proposed.

Physiological and genomic features of Henriciella with the description of Henriciella mobilis sp. nov.

Strains M65T, M69 and JN25 were isolated from seawater of the West Pacific Ocean. Cells of the three strains were Gram-stain-negative, aerobic and rod-shaped. Cells were motile by means of flagella. On the basis of the results of 16S rRNA gene sequence analysis, strains M65T, M69 and JN25 showed the highest 16S rRNA gene sequence similarity to Henriciella algicola MCS27T (98.8 %), followed by Henriciella marina DSM 19595T (98.4 %), Henriciella barbarensis MCS23T (98.4 %), Henriciella pelagia LA220T (98.3 %), Henriciella aquimarina P38T (98.1 %) and Henriciella litoralis SD10T (97.8 %). The 16S rRNA gene sequence similarities among the isolates were 100 %. Phylogenetic analyses revealed that the isolates fell within a cluster comprising the Henriciella species and represented an independent lineage. The average nucleotide identity and in silico DNA-DNA hybridization values between strain M65T and the type strains of Henriciella species were 73.9-85.8 % and 19.9-22.4 %, respectively. The sole respiratory quinone detected in the three isolates was ubiquinone 10. The principal fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C16 : 0. The major polar lipids were glucuronopyranosyldiglyceride, monoglycosyldiglyceride and one unidentified glycolipid. The DNA G+C content was 61.3-61.4 mol%. Phylogenetic distinctiveness, chemotaxonomic differences, together with phenotypic properties, revealed that the isolates could be differentiated from the Henriciella species with validly published names. Therefore, it is proposed that strains M65T, M69 and JN25 represent a novel species of the genus Henriciella, for which the name Henriciella mobilis sp. nov. (type strain, M65T=CGMCC 1.15927T=KCTC 52576T) is proposed.

Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Acute Type A Aortic Dissection Surgery: A Six-Year Experience.

Objectives: Acute type A aortic dissection (aTAAD) is usually lethal without emergency surgery. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in patients with cardiogenic shock following cardiac surgery, VA-ECMO support following aTAAD surgery has not been well-described. Based on our 6-year experience, we aimed to retrospectively analyze risk factors, application and timing of VA-ECMO, and outcomes in aTAAD patients. Methods: In this retrospective, single-center study, we enrolled adult patients who underwent aTAAD surgery from January 2014 to December 2019 and were supported with VA-ECMO. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until discharge. Results: Twenty-seven patients who received aTAAD surgery with VA-ECMO support were included in the study. Nine patients (33.3%) were successfully weaned from VA-ECMO. The median VA-ECMO support time and length of hospital stay in the successfully weaned group were significantly longer than in the group could not be successfully weaned (192 [111-327] vs. 55 [23-95] h, p < 0.01; 29 [18-40] vs. 4 [3-8] days, p < 0.01). Overall in-hospital mortality was 81.5%. The main causes of death were bleeding (37%), neurological complications (15%), and multiple organ dysfunction syndrome (15%). Preoperative levels of creatine kinase-MB (CK-MB) were lower in patients who were successfully weaned from VA-ECMO than in the failed group (14 [6-30] vs. 55 [28-138] U/L, p < 0.01). Postoperative peak levels of CK-MB, cardiac troponin T, lactate dehydrogenase, and lactate were significantly lower in the successful group than in the failed group. Conclusion: Postoperative VA-ECMO support was rarely used in aTAAD patients. Our study showed that VA-ECMO can be considered as a salvage treatment in aTAAD patients, despite the high rate of complications and mortality.

Complete genome sequence of marine Roseobacter lineage member Monaibacterium sp. ALG8 with six plasmids isolated from seawater around brown algae.

Monaibacterium sp. ALG8 (=MCCC 1 K04733) was isolated from seawater around brown algae. The genome of Monaibacterium sp. ALG8 was sequenced, one circular 3,036,380 bp chromosome and six circular plasmids ranging from 12,229 to 151,263 bp were found after assembly. The results of genomic annotation showed that Monaibacterium sp. ALG8 lacks the ability to degrade alginate, indicating its ecological role may not be directly related to the degradation of brown algae. The comparison of genomic features in the plasmids showed that almost all of these plasmids, except pALG4, were horizontally recruited from donors, not ancestors. Based on predicted functions, the existence of plasmids may provide strain ALG8 with advantages including nitrate reduction, tolerance of osmotic stress via glycine betaine, resistance to heavy metal stress such as mercury and cobalt, degradation of benzoate metabolites such as p-cumate, transformation of the swim-or-stick lifestyle and improvement of the immune system with two CRISPR-Cas systems. This study provides evidence for the carbon metabolic patterns of Monaibacterium sp. ALG8 and predicts the functions and donors of six plasmids in this strain, broadening our understanding of the ecological roles of bacteria in the environment around brown algae and the functions and evolutionary patterns of plasmids in marine Roseobacter lineage members.

Mini-invasive surgical instruments in transaortic myectomy for hypertrophic obstructive cardiomyopathy: a single-center experience with 168 cases.

BACKGROUND: Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy. METHODS: Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed. RESULTS: We included 168 eligible patients (83 males, mean 56.8 ± 12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 min. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 22.6 mmHg, p < 0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p < 0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p < 0.001). CONCLUSIONS: Mini-invasive surgical instruments may be beneficial in reducing the technical challenges of transaortic septal myectomy procedure. Of note, transaortic septal myectomy using the mini-invasive surgical instruments may present with favorable results.

Early risk stratification of acute type A aortic dissection: development and validation of a predictive score.

BACKGROUND: The performance of published preoperative risk scores for acute type A aortic dissection (aTAAD) is suboptimal. So, the predictive power of these scores were externally validated in order to develop and validate a more reliable preoperative score for identification of patients at high risk of mortality. METHODS: Potential preoperative risk variables of consecutively admitted patients with aTAAD were prospectively collected. Seven published risk scores were validated with our dataset. For derivation and internal validation, the original population was divided at a ratio of 7:3. Logistic regression was used to identify variables for the new score. A 50-patient retrospective dataset was used for external validation. The predictive accuracy for post-operative mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. RESULTS: During the study period, 225 patients with aTAAD were admitted preoperatively. Of these, 209 underwent surgical repair and 29 died postoperatively. The AUROCs of the seven published pre-operative risk scores for post-operative mortality ranged from 0.57 to 0.77. Four variables were derived for the new score system, i.e., Acute myocardial ischemia, Lactate, Iliac arteries involved, and CreatininE (the ALICE score). The AUROCs for post-operative mortality in the derivation, internal and external validation populations were 0.85, 0.88 and 0.83, respectively. At a cutoff value of 3, the ALICE score for post-operative mortality had a sensitivity of 71% to 88% and specificity of 78% to 86%. CONCLUSIONS: The ALICE score comprising four components might help bedside clinicians in early detection of the most severe aTAAD patients.

Hemodynamic monitoring in patients with venoarterial extracorporeal membrane oxygenation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective mechanical circulatory support modality that rapidly restores systemic perfusion for circulatory failure in patients. Given the huge increase in VA-ECMO use, its optimal management depends on continuous and discrete hemodynamic monitoring. This article provides an overview of VA-ECMO pathophysiology, and the current state of the art in hemodynamic monitoring in patients with VA-ECMO.

Effect of Sequential Noninvasive Ventilation on Early Extubation After Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (aTAAD) is associated with a high incidence of prolonged postoperative invasive mechanical ventilation. We aimed to assess whether sequential noninvasive ventilation (NIV) could facilitate early extubation postoperatively after a spontaneous breathing trial (SBT) failure among aTAAD patients. METHODS: Beginning in December 2016, we transitioned our weaning strategy from repeated SBT until success (phase 1) to extubation concomitant with sequential NIV (phase 2) for subjects who failed their first SBT. The primary outcomes were re-intubation rate, duration of invasive ventilation, and total duration of ventilation. RESULTS: During the study period, 78 subjects with aTAAD failed their first postoperative SBT (38 subjects in phase 1 and 40 subjects in phase 2). Subjects extubated with sequential NIV had shorter median (interquartile range [IQR]) duration of invasive ventilation of 39.5 (30.8-57.8) h vs 89.5 (64-112) h (P < .001) and median (IQR) length of ICU stay of 6 (4.0-7.8) d vs 7.5 (5.8-9.0) d (P = .030). There were no significant differences between the 2 phases with regard to rates of re-intubation (7.5% vs 7.89%, P = .95), tracheostomy (2.5% vs 5.26%, P = .53), and in-hospital mortality (2.5% vs 2.63%, P = .97). CONCLUSIONS: Early extubation followed by sequential NIV significantly reduced duration of invasive ventilation and length of ICU stay without increasing re-intubation rate in postoperative subjects with aTAAD who failed their first SBT.

Contributions of Modifiable Risk Factors to Dementia Incidence: A Bayesian Network Analysis.

OBJECTIVE: To determine and compare the contributions of modifiable risk factors (RFs) with the prevention of dementia in older adults. DESIGN: A systematic review and Bayesian network meta-analysis (NMA). The observational group was set as a reference to collect all existing RFs and compare them with each other. SETTING AND PARTICIPANTS: An exhaustive and comprehensive literature search strategy was used to identify relevant prospective cohort studies from several online databases from their inception to May 1, 2019. Participants without dementia were adults aged greater than 50 years. MEASURES: The required data were extracted from the eligible studies to facilitate the Bayesian NMA. RESULTS: Forty-three cohort studies with 277,294 participants were included in this NMA. Using the observation group as the reference, all defined RFs, except for antioxidants, were associated with lower risks of all-cause dementia [no sleep disturbances (odds ratio, OR 0.43, 95% credible interval, CrI 0.24-0.62), a high level of education (OR 0.50, 95% CrI 0.34-0.66), no history of diabetes (OR 0.57, 95% CrI 0.36-0.78), nonobese patients (OR 0.61, 95% CrI 0.39-0.83), no smoking history (OR 0.62, 95% CrI 0.45-0.79), living with family members (OR 0.67, 95% CrI 0.45-0.89), participation in physical exercise (OR 0.73, 95% CrI 0.46-0.94), abstinence from drinking (OR 0.78, 95% CrI 0.56-0.99), and no history of hypertension (OR 0.80, 95% CrI 0.65-0.96)]. CONCLUSIONS/RELEVANCE: The findings provide reliable support for the hypothesis that modifiable somatic and lifestyle factors are strong predictors of all-cause dementia.

High shear stress suppresses proliferation and migration but promotes apoptosis of endothelial cells co-cultured with vascular smooth muscle cells via down-regulating MAPK pathway.

BACKGROUND: Early neointimal hyperplasia of vein graft may be ameliorated via enhancing intravenous surface shear stress. Cellular processes including proliferation, apoptosis and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) may play very important roles in the process of neointimal hyperplasia of vein graft; and mitogen-activated protein kinase (MAPK) pathways including extracellular signal-regulated kinase (ERK1/2) and p38 pathways play vital roles in regulating a large variety of cellular processes. This study evaluated the impacts of shear stress and MAPK pathways on cellular processes of ECs in a co-culture system with VSMCs, and aimed to test the hypothesis that high shear stress suppresses proliferation and migration but promotes apoptosis of ECs co-cultured with VSMCs via down-regulating MAPK pathway. METHODS: Primary ECs and VSMCs derived from porcine great saphenous vein were collected, respectively. 4-7 generation of cells were used as work cells. ECs and VSMCs were co-cultured and synchronized under high and low shear stress using Parallel-Plate Flow Chamber system. And then, ECs co-cultured with VSMCs were incubated with U0126 (ERK1/2 inhibitor) or PD98059 (p38 inhibitor) under different shear stress. Proliferation, apoptosis and migration of ECs in a co-culture system with VSMCs were detected by 4,5-dimethyl-2-thiazolyl (MTT) assay and bromodeoxyuridine (BrdU) assay, fluorescent-activated cell sorting (FACS) technique, and Transwell assay separately. Each test repeated 3 times. Additionally, protein expressions of ERK1/2 and p38 MAPK were detected by using Western blot, respectively. RESULTS: Under higher level of shear stress condition, proliferation and migration of ECs co-cultured with VSMCs were suppressed, while cell apoptosis was promoted. And blocking ERK1/2 pathway by U0126 or blocking p38 pathway by PD98059, proliferation and migration of ECs co-cultured with VSMCs were further suppressed, while cell apoptosis was further promoted. Additionally, protein expressions of phosphorylation of ERK1/2 and p38MAPK were decreased under higher level of shear stress condition, and were further reduced by blocking ERK1/2 or p38 pathway under shear stress condition. CONCLUSIONS: High shear stress may suppress proliferation and apoptosis of ECs in a co-culture system with VSMCs but promote cell migration via down-regulating ERK1/2 and p38 MAPK pathways.

Preemptive renal replacement therapy in post-cardiotomy cardiogenic shock patients: a historically controlled cohort study.

BACKGROUND: The aim of the study was to evaluate whether the preemptive renal replacement therapy (RRT) might improve outcomes in post-cardiotomy cardiogenic shock (PCCS) patients. METHODS: In Period A (September 2014-April 2016), patients with PCCS received RRT, depending on conventional indications or bedside attendings. In Period B (May 2016-November 2017), the preemptive RRT strategy was implemented in all PCCS patients in our intensive care unit. The goal-directed RRT was applied for the RRT patients. The hospital mortality and renal recovery were compared between the two periods. RESULTS: A total of 155 patients (76 patients in Period A and 79 patients in Period B) were ultimately enrolled in this study. There were no significant differences in demographic characteristics and intraoperative and postoperative parameters between the two groups. The duration between surgery and RRT initiation was significantly shorter in Period B than in Period A [23 (17, 66) vs. 47 (20, 127) h, P<0.01]. The hospital mortality in Period B was significantly lower than that in Period A (38.0% vs. 59.2%, P<0.01). There were fewer patients with no renal recovery in Period B (4.1% vs. 19.4%, P=0.026). Patients in Period B displayed a significantly shorter time to completely renal recovery (12±15 vs. 25±15 d, P<0.05). CONCLUSIONS: Among PCCS patients, preemptive RRT compared with conventional initiation of RRT reduced mortality in hospital and also led to faster and more frequent recovery of renal function. Our preliminary study supposed that preemptive initiation of RRT might be an effective approach to PCCS with acute kidney injury (AKI).