Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report.

BACKGROUND: Ultrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare. CASE PRESENTATION: A 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient's oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient's oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder. CONCLUSIONS: Axillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

[The mechanism of Xuebijing injection in preventing and treating lung injury induced by cardiopulmonary bypass by regulating the apoptosis of alveolar polymorphonuclear neutrophil].

OBJECTIVE: To investigate the protective effect of Xuebijing injection on acute lung injury (ALI) associated with cardiopulmonary bypass (CPB) by regulating the apoptosis of polymorphonuclear neutrophils (PMN). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), CPB model group (CPB group) and Xuebijing pretreatment group (XBJ group) according to the random number table method, with 10 rats in each group. Rats in the CPB group and XBJ group undergoing CPB procedures for 60 minutes. Rats in the Sham group did not undergo CPB. Rats in the XBJ group received intraperitoneal injection of 4 mL/kg Xuebijing injection 2 hours before CPB. Rats in the Sham group and CPB group were injected with an equal amount of normal saline. 4 hours after CPB, arterial blood was collected for blood gas analysis to calculate respiratory index (RI), and lung tissue of rats was collected for determination of lung index (LI) and pulmonary water containing rate. PMN in bronchoalveolar lavage fluid (BALF) were collected and the activity of caspase-3 was detected. The apoptosis rate was detected by flow cytometry. The expressions of microRNA-142-3p (miR-142-3p) and FoxO1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The protein expression of FoxO1 was detected by Western blotting. In addition, HL-60 cells were divided into control oligonucleotide transfection group, miR-142-3p mimics transfection group, and miR-142-3p inhibitor transfection group. After 48 hours of transfection, the activity of miR-142-3p binding to FoxO1 was detected using dual luciferase reporter genes. RESULTS: Compared with Sham group, RI, LI and pulmonary water containing rate were significantly increased in CPB group. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly decreased, the expression of miR-142-3p was decreased, and the expression of FoxO1 protein was increased. However, compared with CPB group, RI, LI and pulmonary water containing rate were significantly decreased in XBJ group [RI: 0.281±0.066 vs. 0.379±0.071, LI: 4.50±0.26 vs. 5.71±0.42, pulmonary water containing rate: (80.31±32.50)% vs. (84.59±3.41)%, all P < 0.01]. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly increased [caspase-3 activity: 0.350±0.021 vs. 0.210±0.014, apoptosis rate: (15.490±1.382)% vs. (8.700±0.701)%, both P < 0.01], the expression of miR-142-3p was significantly up-regulated (2-ΔΔCt: 2.61±0.17 vs. 0.62±0.05, P < 0.01), and the protein expression of FoxO1 was decreased [FoxO1/GAPDH (relative expression level): 0.81±0.04 vs. 1.22±0.06, P < 0.01]. However, there was no statistically significant difference in FoxO1 mRNA expression among the three groups. The bioinformatics analysis results showed that miR-142-3p can bind to the FoxO1 3'untranslated region (3'UTR). In HL-60 cells, compared with control oligonucleotide transfection group, the transfection of miR-142-3p mimics could reduce the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 0.48±0.06 vs. 1.00±0.05, P < 0.01], however, the transfection of miR-142-3p inhibitor increased the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 1.37±0.21 vs. 1.00±0.05, P < 0.05]. But, transfection with miR-142-3p mimics or inhibitor had no effect on FoxO1 mRNA expression. The luciferase reporter gene showed that miR-142-3p could bind to the FoxO1 3'UTR to inhibit FoxO1 expression. CONCLUSIONS: Xuebijing injection may promote the apoptosis of pulmonary alveolar PMN through the miR-142-3p/FoxO1 axis, and play a role in the prevention and treatment of CPB-induced ALI.

Periumbilical giant abscess and intestinal leakage in late pregnancy: A rare case report and literature review.

BACKGROUND: Complicated Periumbilical abscess in late pregnancy is rare in clinical practice. Pubmed searches for articles published from January 1980 to September 2021. Such related reports did not retrieve article about "pregnancy" and "periumbilical abscess." CASE PRESENTATION: We reported on a 34-year-old female patient who was admitted to the hospital with periumbilical pain for 3 days at 34 + 1 weeks of pregnancy. The result of imaging examination showed that there was an inflammatory mass in the middle and lower abdominal wall in the third trimester of pregnancy. The periumbilical abscess was punctured and drained first, and then the pregnant woman was assisted to give birth to a baby girl through vagina after the condition was stable.Subsequently, laparotomy + abdominal abscess resection and drainage + partial small bowel resection + ileostomy were performed. Pathology showed inflammatory mass. CONCLUSIONS: Periumbilical abscess in the third trimester of pregnancy is rare clinically. For some pregnant women with previous trauma and surgical history, obstetric examination should not be restricted. For example, pregnant women with a history of abdominal surgery should expand the range of abdominal color Doppler ultrasound during the prenatal examination. When necessary, combine with computed tomography for diagnosis and treatment, avoid missed diagnosis, which will make the treatment more difficult and increase the risk. If the pregnant women has corresponding symptoms in the third trimester, vaginal delivery can be performed to terminate the pregnancy, and then the periumbilical abscess can be removed. At the same time, closely monitor the vital signs of newborn and mothers.

Prophylactic noninvasive respiratory support in the immediate postoperative period after cardiac surgery - a systematic review and network meta-analysis.

BACKGROUND: Noninvasive respiratory support has been increasingly applied in the immediate postoperative period to prevent postoperative pulmonary complications (PPCs). However, the optimal approach remains uncertain. We sought to evaluate the comparative effectiveness of various noninvasive respiratory strategies used in the immediate postoperative period after cardiac surgery. METHODS: We conducted a frequentist random-effect network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the prophylactic use of noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), or postoperative usual care (PUC) in the immediate postoperative period after cardiac surgery. Databases were systematically searched through September 28, 2022. Study selection, data extraction, and quality assessment were performed in duplicate. The primary outcome was the incidence of PPCs. RESULTS: Sixteen RCTs enrolling 3011 patients were included. Compared with PUC, NIV significantly reduced the incidence of PPCs [relative risk (RR) 0.67, 95% confidence interval (CI): 0.49 to 0.93; absolute risk reduction (ARR) 7.6%, 95% CI: 1.6-11.8%; low certainty] and the incidence of atelectasis (RR 0.65, 95% CI: 0.45 to 0.93; ARR 19.3%, 95% CI: 3.9-30.4%; moderate certainty); however, prophylactic NIV was not associated with a decreased reintubation rate (RR 0.82, 95% CI: 0.29 to 2.34; low certainty) or reduced short-term mortality (RR 0.64, 95% CI: 0.16 to 2.52; very low certainty). As compared to PUC, the preventive use of CPAP (RR 0.85, 95% CI: 0.60 to 1.20; very low certainty) or HFNC (RR 0.74, 95% CI: 0.46 to 1.20; low certainty) had no significant beneficial effect on the incidence of PPCs, despite exhibiting a downward trend. Based on the surface under the cumulative ranking curve, the highest-ranked treatment for reducing the incidence of PPCs was NIV (83.0%), followed by HFNC (62.5%), CPAP (44.3%), and PUC (10.2%). CONCLUSIONS: Current evidence suggest that the prophylactic use of NIV in the immediate postoperative period is probably the most effective noninvasive respiratory approach to prevent PPCs in patients undergoing cardiac surgery. Given the overall low certainty of the evidence, further high-quality research is warranted to better understand the relative benefits of each noninvasive ventilatory support. CLINICAL TRIAL REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022303904.

Successful management of hemodynamic instability secondary to saddle pulmonary embolism-induced cardiac arrest using VA-ECMO in advanced malignancy with brain metastases.

BACKGROUND: Saddle pulmonary embolism (SPE) represents a rare type of venous thromboembolism that frequently causes circulation collapse and sudden death. While venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been well established as a salvage treatment for SPE-induced circulatory shock, it is infrequently administered in patients with advanced malignancy, especially those with brain metastases, given the potential bleeding complications and an uncertain prognosis. As far, there are rare case reports regarding the successful management of hemodynamic instability secondary to SPE-induced cardiac arrest using VA-ECMO in advanced malignancy patients with brain metastases. CASE PRESENTATION: A 65-year-old woman presenting with cough and waist discomfort who had a history of lung cancer with brain metastases was admitted to the hospital to receive chemoradiotherapy. She suffered sudden cardiac arrest during hospitalization and returned to spontaneous circulation after receiving a 10-min high-quality cardiopulmonary resuscitation. Pulmonary embolism was suspected due to the collapsed hemodynamics and a distended right ventricle identified by echocardiography. Subsequent computed tomographic pulmonary angiography revealed a massive saddle thrombus straddling the bifurcation of the pulmonary trunk. VA-ECMO with adjusted-dose systemic heparinization was initiated to rescue the unstable hemodynamics despite receiving thrombolytic therapy with alteplase. Immediately afterward, the hemodynamic status of the patient stabilized rapidly. VA-ECMO was successfully discontinued within 72 h of initiation without any clotting or bleeding complications. She was weaned off invasive mechanical ventilation on the 6th day of intensive care unit (ICU) admission and discharged from the ICU 3 days later with good neurological function. CONCLUSION: VA-ECMO may be a 'bridging' therapy to circulation recovery during reperfusion therapy for SPE-induced hemodynamic collapse in malignancy patients with brain metastases.

Comparison of incidence and prognosis between young and old gastric cancer patient in North-Western China: A retrospective cohort study.

Gastric cancer (GC) is the fourth most common cancer in the world and the second most common cancer in China. In this study, we compared the clinicopathological features and prognosis of GC between young and old patients after curative resection. Six hundred and eighty-six patients with GC resected were divided two groups according to patient age: Younger GC patients ≤40 years of age (YGC, n = 52) and older GC patients >40 years of age (OGC, n = 634). The YGC group had 52 (7.6%) patients in total 686 GC patients. YGC patients was predominant in women (53.8% vs 26.5%) compared with OGC patients. 5-year overall survival exhibited differences in tumor sites, tumor sizes, macroscopic types, T staging, N staging, rate of N staging (rN), tumor node metastasis staging, scope of gastrectomy, radical degree, and lymphatic vascular invasion within each of YGC and OGC group. Univariate analysis of the clinical factors affecting overall survival in YGC group revealed the significant differences in tumor size, macroscopic types (except Borrmann), T staging (except T2), N staging (N3a and N3b), rN, tumor node metastasis staging (III), scope of gastrectomy, radical degree, and lymphatic vascular invasion. Gender, N staging, rN, radical degrees were the independent prognostic factors of younger patients with GC. Similar results were found in the OGC groups. The significant differences in radical degree and lymphatic vascular invasion were found between male and female patients in YGC group. Similar results were found in the OGC groups. Our results showed that YGC patients differ from OGC patients in predominance of women. Gender, N staging, rN, radical degrees were independent risk factors for the prognosis in YGC patients.

RIPK1 is a key factor in black carbon-induced cell death.

Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.

Correlations of preoperative systematic immuno-inflammatory index and prognostic nutrition index with a prognosis of patients after radical gastric cancer surgery.

BACKGROUND: This study aimed to explore the correlations of a preoperative systemic immune-inflammation index and prognostic nutritional index with the prognosis of patients after radical gastric cancer surgery. METHODS: The receiver operating characteristic curve determined the optimal cut-off values of systemic immune-inflammation index, prognostic nutritional index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio. Kaplan-Meier method and Cox proportional hazards model were used to evaluate the correlation between systemic immune-inflammation index, prognostic nutritional index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and patient prognosis. Finally, the receiver operating characteristic curve was adopted to evaluate the efficiency of systemic immune-inflammation index, prognostic nutritional index, and combination of systemic immune-inflammation index and prognostic nutritional index in predicting the prognosis of gastric cancer. RESULTS: We retrospectively analyzed 771 patients from June 2010 to June 2015. The results of Kaplan-Meier analysis showed that the 5-year overall survival was significantly higher in the low systemic immune-inflammation index group than in the high systemic immune-inflammation index group (67.9% vs 28.9%, P < .001), and significantly lower in the low prognostic nutritional index group than in the high prognostic nutritional index group (46.2% vs 74.2%, P < .001). Systemic immune-inflammation index and prognostic nutritional index were independent risk factors for the prognosis of patients with gastric cancer. The results of receiver operating characteristic curve analysis demonstrated that the area under the curve of combining systemic immune-inflammation index and prognostic nutritional index was the largest (area under the curve = 0.747, P < .001), showing statistically significant differences between groups (P < .05), so combining systemic immune-inflammation index and prognostic nutritional index has higher prediction efficiency. CONCLUSION: Systemic immune-inflammation index and prognostic nutritional index are independent risk factors for the prognosis of patients with gastric cancer. The decrease in systemic immune-inflammation index and the increase in prognostic nutritional index suggest a better prognosis, and the combination of systemic immune-inflammation index and prognostic nutritional index can improve the prediction efficiency.

Analysis of safety and efficacy of conservative treatment and endovascular treatment in patients with spontaneous isolated mesenteric artery dissection.

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease with abdominal pain as the main clinical manifestation, but its optimal treatment strategy has not yet been determined. Based on this, this study explored a safe and effective treatment method by analyzing and comparing the safety and efficacy of conservative treatment and endovascular treatment in SISMAD patients. Methods: The clinical and imaging data and treatment effects of 85 patients with SISMAD who were admitted to the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to December 2020 were retrospectively analyzed. Two groups were treated, the data of patients in conservative treatment group and endovascular treatment group were analyzed, and a safe and effective treatment method for SISMAD was discussed. Results: The mean follow-up time was 36.58 ± 25.03 months. The success rate of interventional operation was 86.11% (31/36), and the operation failed because the guide wire could not enter the true lumen in four cases. One case was terminated due to poor physical condition of the patient who could not tolerate surgery. There were no significant differences in gender, body mass index, clinical manifestations, and past history between conservative treatment and endovascular treatment (P > 0.05), but in age, superior mesenteric artery-distal aorta angle, distance from the superior mesenteric artery opening to dissection, dissection length, and true lumen stenosis. There was a statistical difference between the two groups in the rate and Yun classification (P < 0.05). Conclusions: Conservative treatment is effective for most symptomatic SISMAD patients, and close monitoring is required; for patients with persistent symptoms and severe true lumen stenosis (especially Yun classification type III), endovascular treatment is preferred; endovascular treatment is mainly based on endovascular bare stent placement. Patients receiving stent implantation may suffer from stent stenosis or occlusion in the long term, and most of them have no obvious symptoms of intestinal ischemia; the prognosis is good.

Assessment of changes in genetic transcriptome in nasal epithelial cells exposed to ozone-aged black carbon and pollen allergen by high-throughput transcriptomics.

BACKGROUND: Air pollution may be associated with increased airway responsiveness to allergens in allergic rhinitis (AR). Ozone-aged environmental black carbon (O3BC) is an important constituent of atmospheric particulate matter (PM), for which the mechanisms underlying its effects have not been fully elucidated in AR. The objective of the present study was to determine the O3BC and pollen-induced alterations in the transcriptome in human nasal epithelial cells (hNECs) in vitro. METHODS: hNECs from nasal epithelial mucosal samples of healthy individuals undergoing nasal surgery (turbinoplasty or septoplasty) were established as air-liquid interface (ALI) cultures and exposed to O3BC, pollen, or a combination of O3BC+ pollen. Changes in cell viability were analyzed by fluorescence and changes in the transcriptome by high-throughput RNA sequencing (RNA-seq). Several differentially expressed genes were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Enrichment analysis, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, was performed to determine major biological functions and pathways involved. RESULTS: Exposure to ≥ 50 µg/ml O3BC or 25 µg/ml O3BC+ 200 µg /ml pollen significantly decreased cell viability of the hNECs compared to control (p < 0.05) or 25 µg/ml O3BC alone (p < 0.05); whereas exposure to pollen alone did not alter cell viability at any concentration investigated. High-throughput RNA sequencing analysis indicated that there was significant difference in gene expression between pollen or O3BC alone and O3BC+ pollen exposed cells. Exposure to 200 µg/ml O3BC was associated with hypoxia stress response GO terms, whereas exposure to 25 µg/ml O3BC+ 200 µg/ml pollen was associated with inflammatory response GO terms; including regulation of neutrophil migration and chemotaxis, macrophage differentiation and chemotaxis, mast cell activation, and phagocytosis. KEGG pathway analysis indicated the top 10 upstream regulators to be IL1B, CSF1, CCL2, TLR2, LPL, IGF8, SPP1, CXCL8, FCER1G and IL1RN; of which expressions of inflammation-related genes IL1B, CSF1 and FCER1G were significantly increased. CONCLUSION: O3BC and pollen allergen combined exposure may induce innate immune and allergic inflammation in hNECs, and therefore potentially exacerbate the symptoms of AR in affected individuals.

Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)-nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1-interleukin 1ß (IL-1ß) pathway.

BACKGROUND: Allergic rhinitis(AR) is an increasing challenge to public health worldwide. Exposure to environmental black carbon (BC) is associated with increased risk of allergic rhinitis, but the molecular mechanisms underlying its toxicity have not been fully elucidated. The aims of the present study were therefore to determine the effect of BC on the expression of interleukin 1ß (IL-1ß) and to investigate the mechanism underlying BC-induced IL-1ß production in pollen-sensitized human nasal epithelial cells (hNECs). METHODS: Nasal mucosal samples collected from 10 patients undergoing nasal surgery were used to isolate and culture epithelial cells as air-liquid interface (ALI) cultures. Cultures exposed to BC ± pollen allergen for 24 hours were assessed for the presence of IL-1ß, the production of reactive oxygen species (ROS), and activation of the nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, the mechanisms underlying BC ± pollen allergen-induced IL-1ß in hNECs were evaluated. RESULTS: Exposure to BC significantly increased the production of IL-1ß and ROS and the expression of NLRP3 in hNECs, compared with control, all of which were significantly increased further by exposure to a combination of BC and pollen. Incubation of hNECs with N-acetyl-L-cysteine (NAC) significantly attenuated BC ± pollen-induced expression of ROS, NLRP3, and IL-1ß. NLRP3 and Caspase-1 inhibitors (MCC950 and YVAD) significantly inhibited IL-1ß expression and NLRP3 activation, but not NLRP3 expression following exposure to BC ± pollen. CONCLUSION: These findings suggest that exposure to BC and pollen can exaggerate oxidative stress and significantly increase the expression of IL-1ß in hNECs, and that this may involve a pathway integrating ROS-NLRP3-Caspase-1-IL-1ß signaling.

Inhibition of CXCL1-CXCR2 axis ameliorates cisplatin-induced acute kidney injury by mediating inflammatory response.

One of the limiting side effects of cisplatin use in cancer chemotherapy is nephrotoxicity. Inflammation is now believed to play a major role in the pathogenesis of cisplatin-induced acute kidney injury (AKI), and the mediators of inflammation contribute to it. CXCL1 was recently reported to be involved in renal physiology and pathology in ischemia mouse model; however, its roles and mechanisms in cisplatin-induced AKI are completely unknown. We observed that CXCL1 and CXCR2 expression in the kidney was markedly increased on day 7 after cisplatin treatment. Subsequently, we demonstrate that inhibition of CXCL1-CXCR2 signaling axis, using genetic and pharmacological approaches, reduces renal damage following cisplatin treatment as compared with control mice. Specifically, deficiency of CXCL1 or CXCR2 extensively preserved the renal histology and maintained the kidney functions after cisplatin treatment, which was associated with reduced expression of the pro-inflammatory cytokines and infiltration of neutrophils in the kidneys as compared. Furthermore, inhibition of CXCR2 by intragastric administration of repertaxin in mice with AKI reduces kidney injury associated with a reduction of inflammatory cytokines and neutrophils infiltration. Finally, we found that CXCL1/CXCR2 regulated cisplatin-induced inflammatory responses via the P38 and NF-κB signaling pathways in vitro and in vivo. In conclusion, our results indicate that CXCL1-CXCR2 signaling axis plays a crucial role in the pathogenesis of cisplatin-induced AKI through regulation of inflammatory response and maybe a novel therapeutic target for cisplatin-induced AKI.

[To explore the preventive and therapeutic effects of Xuebijing injection on acute lung injury induced by cardiopulmonary bypass in rats by regulating the expression of microRNA-17-5p and its mechanism].

OBJECTIVE: To investigate the preventive effect of Xuebijing injection on acute lung injury induced by cardiopulmonary bypass (CPB) and the underlying mechanism. METHODS: (1) In vivo experiment: 30 Sprague-Dawley (SD) rats were randomly divided into sham group, CPB group, Xuebijing pretreatment group (XBJ+CPB group) with 10 rats in each group. CPB model was reproduced in rats; and CPB was not performed in sham group, but only through arteriovenous puncture. In the XBJ+CPB group, 4 mL/kg Xuebijing injection was injected intraperitoneally 2 hours before CPB, sham group and CPB group were injected with equal volume of normal saline at the same time. The blood from femoral artery was analyzed 4 hours after operation, and the oxygenation index (PaO2/FiO2) was calculated. Then the rats were sacrificed to collect bronchoalveolar lavage fluid (BALF), and the lung permeability index (PPI) was calculated. The lung tissues were harvested, and the wet/dry weight ratio (W/D) of lung tissue was measured. The index of quantitative evaluation of alveolar injury (IQA) was measured. The levels of interleukins (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) in lung tissue and BALF were measured by enzyme-linked immunosorbent assay (ELISA). The content of malondialdehyde (MDA) and the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in lung tissue were detected by biochemical method. The microRNA-17-5p (miR-17-5p) expression in lung tissue was determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). (2) In vitro experiments: type II alveolar epithelial cells (AEC II) were cultured in vitro, and they were randomly divided into control group (the cells were treated by preoperative serum of CPB in patients with ventricular septal defect), CPB group (the cells were treated by serum after CPB in patients), and XBJ+CPB group (Xuebijing injection 10 g/L+serum after CPB in patients). After 12 hours of culture in each group, the expression of miR-17-5p was detected by RT-qPCR. AEC II cells were transfected with miR-17-5p mimic, inhibitor or corresponding control oligonucleotide (negative control), respectively, to observe the effect of miR-17-5p on Xuebijing regulating CPB-induced apoptosis rate and caspase-3 activity. RESULTS: (1) In vivo experiment: compared with the sham group, the PPI, lung W/D ratio, IQA, and IL-1, IL-6, TNF-α in lung tissue and BALF, as well as MDA content and MPO activity in lung tissue were significantly increased, PaO2/FiO2 and SOD activity in lung tissue were significantly decreased. The parameters of the XBJ+CPB group were significantly improved, suggesting that Xuebijing pretreatment could improve CPB-induced ALI in rats. The expression of miR-17-5p in lung tissue of the CPB group was significantly down-regulated as compared with sham group (2-ΔΔCt: 0.48±0.13 vs. 1.00±0.11, P < 0.05); while the expression of miR-17-5p in the XBJ group was significantly up-regulated as compared with the CPB group (2-ΔΔCt: 1.37±0.09 vs. 0.48±0.13, P < 0.05), indicating that the improvement of Xuebijing injection on lung injury after CPB might be related to miR-17-5p. (2) In vitro experiment: the changes in miR-17-5p expression in each group of AEC II cells confirmed in vivo results. After transfection of miR-17-5p mimic, the apoptotic rate and caspase-3 activity of each group were significantly lower than those transfected with negative control, and the decrease was more significant in the XBJ+CPB group [apoptotic rate: (7.37±0.95)% vs. (12.60±1.90)%, caspase-3 (A value): 0.82±0.09 vs. 1.37±0.08, both P < 0.05]. After transfection of miR-17-5p inhibitor, the apoptotic rate and caspase-3 activity of each group were significantly more than those transfected with negative control [in the XBJ+CPB group: apoptotic rate was (16.30±1.86)% vs. (12.60±1.90)%, caspase-3 (A value) was 1.78±0.13 vs. 1.37±0.08, both P < 0.05]. This indicated that the apoptosis of AEC II cells cultured in serum after CPB was significantly reduced by miR-17-5p, and further reduced by the pretreatment with Xuebijing. CONCLUSIONS: Xuebiing injection can reduce the inflammatory reaction and oxidative stress of lung tissue in rats with ALI induced by CPB, and improve oxygenation. The mechanism may be related to up-regulation of miR-17-5p expression in AEC II cells and inhibition of apoptosis of AEC II cells.

Strategically prolonged release of multiple antibacterial components from a thin film coating for synergistic effects against Staphylococcus aureus infections.

Biomaterial-associated infections (BAIs) remain a major challenge in clinical surgery because they can potentially cause serious disabilities in patients. This study investigated the use of a multilayer coating technology that can co-deliver two therapeutic components, gentamicin and OP-145 peptide, to treat Staphylococcus aureus effectively. A biocompatible and biodegradable thin film was produced via layer-by-layer assembly using an antibacterial peptide and gentamicin. The thin film was systematically characterized, showing controllable features such as thickness, transparency, cargo loading, and cargo release. In vitro tests showed that the thin film has fewer toxicity problems than soluble cargos; compared to cargos in a soluble form, the thin film has minor impacts on mammalian cells' metabolism. Additionally, the antibacterial cargos assembled on the thin film can effectively inhibit the formation of biofilms and show effective in vitro antibacterial potency. In vivo studies illustrated that the thin film can inhibit the progression of S. aureus in a mouse model, indicating the effectiveness of the thin film structure in the clinic. This study demonstrates that a thin film composed of gentamicin and OP-145 could be employed to prevent BAIs in clinical surgery.

Effect of levosimendan on clinical outcomes in adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

It is currently unknown whether levosimendan can improve clinical outcomes in patients undergoing cardiac surgery. This meta-analysis aimed to assess the effect of levosimendan on mortality and the duration of intensive care unit (ICU) and hospital stay in adult patients undergoing cardiac surgery. A comprehensive search for eligible articles was conducted in PubMed, OVID and Cochrane databases of clinical trials and the Web of Science from database inception to August 2017. Stata/SE 11.0 was used to calculate the pooled odds ratio for postoperative mortality and the pooled standardized mean difference (SMD) for the duration of ICU stay and hospital stay. A total of 30 randomized controlled trials were included in the final analysis; the pooled results indicated that perioperative administration of levosimendan was associated with a reduction in postoperative mortality [5.8% vs 8.5%; odds ratio 0.66, 95% confidence interval 0.50-0.86, P = 0.002; I2 = 17.1%; 25 trials; 3239 patients] and length of ICU stay (SMD -0.32, 95% CI -0.58 to 0.06, P = 0.017; I2 = 88.0%; 23 trials; 2536 patients) compared with the control group but not in length of hospital stay (SMD -0.41, 95% CI -0.89 to 0.07, P = 0.094; I2 = 95.9%; 18 trials; 2047 patients). A subanalysis was conducted for trials published after 2015, and it suggested that levosimendan could not reduce the postoperative mortality (odds ratio = 0.91, 95% CI 0.63-1.31, P = 0.626; I2 = 0.9%), length of ICU stay (SMD -0.03, 95% CI -0.32 to 0.27, P = 0.850; I2 = 81.2%) or length of hospital stay (SMD 0.06, 95%CI -0.43 to 0.54, P = 0.821; I2 = 91.3%). To summarize, the evidence from studies published in the last 3 years indicated that perioperative administration of levosimendan was not associated with better clinical outcomes in adult patients undergoing cardiac surgery.

[Effects of interleukin-34 expressed by human bone marrow derived mesenchymal stem cells on THP-1 cells].

To construct recombinant eukaryotic expression plasmid vector of human IL-34 gene, and to study the effects of IL-34 expressed by human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on THP-1 cells. Full-length IL-34 encoding sequence was amplified by PCR. And this fragment was cloned into the plasmid pIRES2-EGFP. Western blotting and ELISA were used to analyze the expression of IL-34 in hBM-MSCs. THP-1 cells were cultured with hBM-MSCs medium containing IL-34 protein. Real-time PCR detected the effects of IL-34 on the expression of IL-10 and TNFα in THP-1 cells. Restrictive enzyme analysis and sequencing demonstrated that IL-34 eukaryotic expression vector was successfully constructed. IL-34 protein expressed by hBM-MSCs could promote IL-10 and TNFα expression in THP-1 cells. Those results show that IL-34 expressed by hBM-MSCs has regulating effect on THP-1 cells.

MicroRNA-34a Suppresses Autophagy in Alveolar Type II Epithelial Cells in Acute Lung Injury by Inhibiting FoxO3 Expression.

Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined. Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. The effects of miR-34a on its target gene, FoxO3, in regulating autophagic activity in AT-II cells were also determined. LPS induced autophagic activity and increased the expression of miR-34a in lung tissues and in AT-II cells. The in vitro results showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in AT-II cells. Moreover, miR-34a could directly bind to the 3'-untranslated region of the autophagy-related gene, FoxO3, to decrease its expression. In addition, the knockdown of FoxO3 expression inhibited the autophagic activity in AT-II cells. Together, this study suggested that miR-34a might suppress the excessive autophagic activity in AT-II cells via targeting FoxO3 to reduce the damage of LPS-induced ALI.

The microRNA miR-17 regulates lung FoxA1 expression during lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a severe pulmonary disease that causes a high number of fatalities worldwide. Studies have shown that FoxA1 expression is upregulated during ALI and may play an important role in ALI by promoting the apoptosis of alveolar type II epithelial cells. However, the mechanism of FoxA1 overexpression in ALI is unclear. In this study, an in vivo murine model of ALI and alveolar type II epithelial cells injury was induced using lipopolysaccharide (LPS). LPS upregulated FoxA1 in the lung tissue of the in vivo ALI model and in LPS-challenged type II epithelial cells. In contrast, miR-17 was significantly downregulated in these models. After miR-17 antagomir injection, the expression of FoxA1 was significantly increased in ALI mice. MiR-17 mimics could significantly inhibit FoxA1 mRNA and protein expression, whereas the miR-17 inhibitor could significantly increase FoxA1 mRNA and protein expression in LPS-induced type II epithelial cells. Thus, our results suggest that the downregulation of miR-17 expression could lead to FoxA1 overexpression in ALI.

Forkhead box protein A1 inhibits the expression of uncoupling protein 2 in hydrogen peroxide-induced A549 cell line.

Forkhead box protein A1 (FoxA1) is a transcription factor that is involved in embryonic development and cell differentiation. In this study, we show that hydrogen peroxide (H2O2) treatment upregulated expression of FoxA1 and UCP2 in the A549 cell line. Overexpression of FoxA1 by full-length complementary DNA reduced UCP2 expression, while silencing of FoxA1 expression by small interfering RNA significantly increased UCP2 levels. FoxA1 binds to a site from -919 to -913 bp relative to the UCP2 transcription start site. The overexpression of FoxA1 promoted the DNA binding activity and attenuated the transcription of UCP2 promoter as shown by electromobility shift, chromatin immunoprecipitation assays, and luciferase reporter assay. These data indicate an important role of FoxA1 in regulating expression of UCP2.

The performance of photooxidatively crosslinked acellular bovine jugular vein conduits in the reconstruction of connections between pulmonary arteries and right ventricles.

In this study, valved photooxidatively crosslinked acellular bovine jugular vein conduits (BJVCs) were implanted in young dogs to reconstruct the connections of pulmonary arteries and right ventricles, with acellular conduits used as controls. All acellular conduits had moderate to severe valvular dysfunction and were explanted at 1-month implantation (n = 5). Histological examination showed inflammatory cell infiltration and intimal hyperplasia in the walls, and severe inflammatory cell infiltration and thrombosis in the valves. The photooxidatively crosslinked acellular conduits were retrieved at 1-month (n = 5) and 6-month (n = 5) implantations respectively. These conduits had excellent valvular function at retrieval. Their walls and valves were still soft and smooth without calcification and hemangioma. Endothelialization in valves and luminal walls was unsatisfied at 1-month retrieval, and was improved at 6-month retrieval. Host cells infiltrated and migrated from outer layer to the middle layer, with tissue remolding and regeneration found in these recellular regions. Histological examination and tissue content assay demonstrated that degeneration and regeneration of collagens and glycosaminoglycans were comparable, but elastic fibers gradually degraded. Photooxidatively crosslinked acellular BJVCs resist calcification and thrombosis and have regeneration patterns, with excellent hemodynamic performance.