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To clarify the evolution of “production-living-ecological” function coupling in the Yellow River Basin, coordinating the spatial allocation of resources, development management and layout optimization, is an important means for achieving ecological protection and high-quality development in the region. In this paper, we conducted an empirical analysis and ARIMA prediction of the coupled production-living-ecological function coordination level in the Yellow River Basin of China from 2008 to 2018, and found that: (1) In terms of temporal evolution, the production-living-ecological function and coupling coordination level of each province and region in the Yellow River Basin generally shows a sharp and then slow upward trend, with the living functions changing more than the production and ecological functions; (2) in terms of spatial pattern, the production and living functions of each province and region show the trend of functional level increasing from east to west over time; the ecological functions, contrary to production and living functions, show a “high-low” aggregation, midstream shows “low-low” aggregation, and downstream shows “low-high” aggregation; (3) According to the regression results of the spatial Dubin model, the environmental governance level, technological research and development level, and social security level and resource dependence degree have positive promoting and spillover effects on the coupling coordination level of the “production-living-ecological” function in the region. However, population density and carbon emission intensity will hinder the development of regional coupling coordination level; (4) from the ARIMA prediction, the coupling coordination level of “production-living-ecological” in the Yellow River Basin continues the development trend of 2008–2018 in the short term, the overall coordination level is at a high level, and the variability of coupling coordination level among provinces and regions is further reduced. Finally, corresponding development countermeasures and suggestions are given to different provinces and regions based on the spatial and temporal evolution characteristics, influencing factors and development trend of the “production-living-ecological” function in the Yellow River basin.

Background: c-Jun N-terminal kinase 1 (JNK1) and JNK2 regulate distinct pathological processes in lung diseases. Here we discriminated the respective roles of these kinases in lung transplantation-induced ischemia-reperfusion injury (IRI). Methods Rat pulmonary microvascular endothelial cells were transfected with JNK1 small-interfering RNA (siRNA) and JNK2 siRNA and then subjected to in vitro IRI. For the isoform confirmed to aggravate IRI, the delivery of short-hairpin RNA (shRNA) plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. After a 3-hour reperfusion, the samples were collected. Results JNK1 siRNA decreased but JNK2 siRNA increased JNK phosphorylation and activity, phosphorylated and total c-Jun, and activator protein-1 activity. Although JNK1 siRNA decreased apoptosis and the levels of malondialdehyde, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α), it increased the levels of superoxide dismutase, S-phase percentage, and cyclin D1; JNK2 siRNA had a converse effect. JNK1 siRNA decreased the level of lactate dehydrogenase and increased the levels of VE-cadherin, nitric oxide, phosphorylated nitric oxide synthase, and cell viability; JNK2 si RNA had a converse effect. Compared with the control group, the JNK1 shRNA group exhibited a higher lung oxygenation index and lower lung apoptosis index, injury score, wet weight:dry weight ratio, and levels of IL-1, IL-6, and TNF-α. Conclusions JNK1 aggravated, but JNK2 alleviated, IRI through differential regulation of the JNK1 pathway in in vitro ischemia-reperfusion. JNK1 silence attenuated lung graft dysfunction by inhibiting inflammation and apoptosis. These findings provide a theoretical basis for devising therapeutic strategies against IRI after lung transplantation.

Cerebral ischemia/reperfusion injury (CIRI) is closely related to mitochondrial dysfunction in astrocytes. Therefore, based on glucose transporter 1 (GLUT1), which is highly expressed in the brain tissue of rats with CIRI, we design a kind of brain-targeted dexmedetomidine (Man@Dex) nanomicelles. The results showed that Man@Dex not only had the advantages of small particle size, stability and non-toxicity, but also realized brain-targeted drug delivery. Primary astrocytes were cultured in vitro to construct CIRI cell model. It was found that Man@Dex could improve the activity of injured astrocytes. Man@Dex could exert antioxidant activity by inhibiting the reactive oxygen species (ROS) production of astrocytes, thus inhibiting the cytotoxicity induced by hypoxia and reoxygenation. Man@Dex could improve the ATP level and mitochondrial membrane potential (MMP) to protect mitochondrial function of damaged astrocytes. The CIRI rat model was constructed and confirmed by hematoxylin and eosin (HE), Triphenyl-2H-tetrazolium chloride (TTC) staining and nerve defect score. It indicated that Man@Dex could alleviate CIRI and improve MMP, which was beneficial to the recovery of brain injury in rats. This research provides a new theoretical basis and target for the development of brain-targeted nano-drugs of CIRI.

Lung ischemia-reperfusion injury is a complex pathophysiologic process associated with high morbidity and mortality. We have demonstrated elsewhere that diabetes mellitus aggravated ischemia-induced lung injury. Oxidative stress and mitochondrial dysfunction are drivers of diabetic lung ischemia-reperfusion injury; however, the pathways that mediate these events are unexplored. In this study using a high-fat diet-fed model of streptozotocin-induced type 2 diabetes in rats, we determined the effect of hydrogen sulfide on lung ischemia-reperfusion injury with a focus on Sirtuin3 signaling.Rats with type 2 diabetes were exposed to GYY4137, a slow release donor of hydrogen sulfide with or without administration of the Sirtuin3 short hairpin ribonucleic acid plasmid, and then subjected to a surgical model of ischemia-reperfusion injury of the lung (n = 8). Lung function, oxidative stress, inflammation, cell apoptosis, and mitochondrial function were measured.Compared with nondiabetic rats, animals with type 2 diabetes at baseline exhibited significantly decreased Sirtuin3 signaling in lung tissue and increased oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction (P.05 each). In addition, further impairment in Sirtuin3 signaling was found in diabetic rats subjected to this model of lung ischemia-reperfusion. Simultaneously, the indexes showed further aggravation. Treatment with hydrogen sulfide restored Sirtuin3 expression and decreased lung ischemia-reperfusion injury in animals with type 2 diabetes mellitus by improving lung functional recovery, decreasing oxidative damage, suppressing inflammation, ameliorating cell apoptosis, and preserving mitochondrial function (P.05). Conversely, these protective effects were largely reversed in Sirtuin3 knockdown rats.Impaired lung Sirtuin3 signaling associated with type 2 diabetic conditions was further attenuated by an ischemia-reperfusion insult. Hydrogen sulfide ameliorated reperfusion-induced oxidative stress and mitochondrial dysfunction via activation of Sirtuin3 signaling, thereby decreasing lung ischemia-reperfusion damage in rats with a model of type II diabetes.

Background Hypercapnia alleviates pulmonary ischemia–reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Methods Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague–Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague–Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. Results The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8+ T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4+ T cells, and interleukin-10 levels were similar between groups. Conclusions Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

Background Hydrogen sulfide attenuates lung ischemia-reperfusion injury when inhaled or administered intraperitoneally. This study investigated the effects of lung inflation with H 2 S during the warm ischemia phase on lung grafts from rat donors after cardiac death. Methods One hour after cardiac death, donor lungs were inflated in situ for 2 h with either O 2 or H 2 S (O 2 or H 2 S group) during the warm ischemia phase or were deflated as a control procedure ( n = 8). After 3 h of cold preservation, lung transplantation was performed. During the warm ischemia phase, the metabolism and mitochondrial structures of donor lungs were analyzed. Arterial blood gas analysis was performed on the recipients. Protein expression in the graft of nuclear factor E2-related factor (Nrf)2 and nuclear factor kappa B (NF-κB) was analyzed by Western blotting, and static compliance, inflammation, oxidative stress, and cell apoptosis were assessed after 3 h of reperfusion. Results When the O 2 and H 2 S groups were compared with the control group, the mitochondrial structures were improved, and lactic acid levels, inflammation, oxidative stress, and cell apoptosis were significantly decreased; and glucose levels, as well as graft oxygenation and static compliance were increased. Simultaneously, the above indices showed further improvements, and the Nrf2 protein expression was significantly greater, and NF-κB protein expression was less in the H 2 S group than the O 2 group. Conclusion Lung inflation with H 2 S during the warm ischemia phase inhibited metabolism in donor lungs via mitochondrial protection, attenuated graft ischemic-reperfusion injury, and improved graft function through NF-κB-dependent anti-inflammatory and Nrf2-dependent antioxidative and antiapoptotic effects.

BACKGROUND Lung injury after cardiopulmonary bypass (CPB) is a serious postoperative complication and can affect the postoperative recovery. The purpose of this study was to explore whether erythropoietin (EPO) has an effect on lung injury caused by CPB. MATERIAL AND METHODS Sixty patients who received the CPB were randomly divided into a saline group and the EPO group. All the patients received saline or EPO preoperatively, respectively. The ventilation function, including dynamic compliance, peak airway pressure, and plateau pressure, were recorded. The level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1s, and IL-10 in serum and arterial blood gas were analyzed. The mechanical ventilation time in the intensive care unit (ICU), the length of time spent in the ICU, the time from operation to discharge, and the total time of hospitalization were recorded. Adverse events in the ICU were monitored and recorded. RESULTS EPO significantly decreased the level of TNF-alpha and IL-1s, but increased the level of IL-10 after CPB. EPO significantly improved pulmonary ventilated function and gas exchange function after CPB. EPO significantly shortened the mechanical ventilation time and stay in the ICU. CONCLUSIONS Preoperative EPO injection reduced lung injury and promoted lung function in patients who underwent CPB. The protection effect of EPO may be associated with inhibition of inflammatory response.

Background: We have previously shown that epidural dexmedetomidine, when used as an adjunct to levobupivacaine for control of postoperative pain after open colonic resection, improves recovery of gastrointestinal motility compared with morphine. Methods: Sixty patients undergoing laparoscopic colonic resection were enrolled and allocated randomly to treatment with dexmedetomidine (group D) or morphine (group M). Group D received an epidural loading dose of dexmedetomidine (5 mL, 0.5 μg/kg), followed by continuous epidural administration of dexmedetomidine (80 μg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Group M received an epidural loading dose of morphine (5 mL, 0.03 mg/kg) followed by continuous epidural administration of morphine (4.5 mg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Verbal rating score (VRS) of pain, postoperative analgesic requirements, side effects related to analgesia, and time to postoperative first flatus (FFL) and first feces (FFE) were recorded. Results: VRS and postoperative analgesic requirements were not significantly different between the treatment groups. In contrast, FFL and FFE were significant delayed in group M compared with group D (P

Oral squamous cell carcinoma (OSCC) is the most common type and most threatening head and neck cancer worldwide. Here, we aim to study the relationship between the WNT7A-β-Catenin signaling pathway and the chemotherapy resistance of OSCC patients. We analyzed 42 OSCC patients and 19 adjacent non-tumor tissues, evaluated the expression levels of WNT7A mRNA, and subsequently studied WNT7A dependent cisplatin resistance in OSCC cell line KB cells. Moreover, we also utilized an in vivo mouse model to validate our findings. We first found a significant upregulation of WNT7A mRNA in OSCC patients. Our results showed that the knockdown of WNT7A sensitized KB cells to cisplatin. Moreover, our results revealed that nuclear β-catenin was dramatically reduced and cleaved caspase-3 and cleaved PARP were dramatically induced when WNT7A was knocked down in cisplatin treated KB cells. Besides, we found that the knockdown of WNT7A significantly reduced the weight and volumes of xenograft tumors. Moreover, we examined apoptotic cells and found that the combination of WNT7A knockdown and cisplatin treatment resulted in many more apoptotic cells than cisplatin treatment alone, suggesting that the knockdown of WNT7A sensitized KB cells to cisplatin treatment in vivo. Our results revealed that inhibition of WNT7A-β-catenin signaling sensitizes OSCC to cisplatin, which has provided insights into the molecular diagnosis and treatment of OSCC.

Cardiopulmonary bypass can result in lung injury. This prospective, double-blinded, randomized trial aimed to evaluate the protective effect of inhaled budesonide on lung injury after cardiopulmonary bypass.Sixty patients, aged 25 to 65 years, requiring cardiopulmonary bypass were randomized to groups treated with saline or budesonide inhalation preoperatively. The respiratory mechanics were recorded. Bronchoalveolar lavage fluid was collected before cardiopulmonary bypass and after sternal closure. Serum and bronchoalveolar lavage fluid levels of proinflammatory and anti-inflammatory factors were analyzed. The primary end point was the lowest ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen after cardiopulmonary bypass. The durations of ventilation and postoperative recovery time were noted.Budesonide significantly improved respiratory mechanics after cardiopulmonary bypass. Budesonide improved the partial pressure of arterial oxygen to the fraction of inspired oxygen ratio from 8 to 48 hours after the operation. Budesonide shortened the durations of mechanical ventilation and postoperative recovery time. Budesonide decreased the levels of proinflammatory factors while increasing the levels of anti-inflammatory factors in bronchoalveolar lavage fluid and serum (all P .05). The macrophage and neutrophil counts, and protein and elastase concentrations were decreased by budesonide treatment.Budesonide treatment shortened the durations of mechanical ventilation, inhibited local and systemic inflammation, and improved respiratory function after cardiopulmonary bypass.

Objective Endothelial progenitor cells (EPCs) can improve endothelial integrity. This study aimed to examine the effects and the mechanism of EPCs on lung ischemia-reperfusion injury (LIRI). Methods Wistar rats were randomized into the sham or the left lung transplantation group. The recipients were randomized and treated with vehicle as the LIRI group, with EPC as the EPC group, or with N5-(1-iminoethyl)-l-ornithine-pretreated EPC as the EPC/L group (n = 8 per group). The ratios of arterial oxygen partial pressure to fractional inspiratory oxygen were measured. The lung wet-to-dry weight ratios, protein levels, and injury, as well as the levels of plasma cytokines, were examined. The levels of endothelin (ET)-1, endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, inducible NOS, phosphorylated myosin light chain, nuclear factor-κBp65, Bax, Bcl-2, cleaved caspase-3, and myeloperoxidase in the graft lungs were detected. Results Compared with the LIRI group, EPC treatment significantly increased the ratios of arterial oxygen partial pressure to fractional inspiratory oxygen and decreased the lung wet-to-dry weight ratios and protein levels in the grafts, accompanied by increasing eNOS expression and phosphorylation, but decreasing endothelin-1, inducible NOS, phosphorylated nuclear factor-kBp65, phosphorylated myosin light chain expression, and myeloperoxidase activity. EPCs reduced lung tissue damage and apoptosis associated with decreased levels of Bax and cleaved caspase-3 expression, but increased Bcl-2 expression. EPC treatment significantly reduced the levels of serum proinflammatory factors, but elevated levels of interleukin-10. In contrast, the protective effect of EPCs were mitigated and abrogated by N5-(1-iminoethyl)-l-ornithine pretreatment. Conclusions Data indicated that EPC ameliorated LIRI by increasing eNOS expression.

The inhibition of mitogen‑activated protein kinases (MAPKs), including c‑Jun NH2‑terminal protein kinase (JNK), p38 MAPK (p38) and extracellular signal‑regulated protein kinase 1/2 (ERK1/2), have an important effect on lung ischemia‑reperfusion injury (IRI) during lung transplantation (LT). However, the way in which combined MAPK inhibition exerts optimal protective effects on lung IRI remains to be elucidated. Therefore, the present study evaluated the therapeutic efficacy of the inhibition of MAPKs in rat pulmonary microvascular endothelial cells (PMVECs) in an IRI model of LT. The rat PMVECs were transfected with small interfering RNAs (siRNAs) against JNK, p38 or ERK1/2. Cotransfection was performed with siRNAs against JNK and p38 in the J+p group, JNK and ERK1/2 in the J+E group, p38 and ERK1/2 in the p+E group, or all three in the J+p+E group. Non‑targeting (NT) siRNA was used as a control. The PMVECs were then treated to induce IRI, and the levels of inflammation, apoptosis and oxidative stress were detected. Differences between compared groups were determined using Tukey's honest significant difference test. In all groups, silencing of the MAPKs was shown to attenuate inflammation, apoptosis and oxidative stress to differing extents, compared with the NT group. The J+p and J+p+E groups showed lower levels of interleukin (IL)‑1β, IL‑6 and malondialdehyde, a lower percentage of early‑apoptotic cells, and higher superoxide dismutase (SOD) activity, compared with the other groups. No significant differences were observed in the inflammatory response, SOD activity or early apoptosis between the J+p and J+p+E groups. These findings suggested that the dual inhibition of JNK and p38 led to maximal amelioration of lung IRI in the PMVECs of the IRI model of LT, which occurred through anti‑inflammatory, anti‑oxidative and anti‑apoptotic mechanisms.

Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via inhalation, and as an additive dissolved in flush/preservation solution. This study observed the effects of lung inflation with CO on lung graft function in the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60% nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group) during the cold ischemia phase and were kept at 4℃ for 180 min. Recipients were sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham group had no transplantation and were performed as the recipients. Compared with the sham group, the oxygenation determined by blood gas analysis and the pressure–volume curves of the lung grafts decreased significantly, while the wet weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell apoptosis increased markedly ( P

Lung ischemia-reperfusion injury (LIRI) is a pathologic process that is observed in several clinical conditions, and p38 mitogen-activated protein kinase (MAPK) is involved. Diabetes mellitus (DM) results in an increased incidence of ischemia-induced organ damage. The aims of this study were to examine the effects of DM on LIRI in a rat model of DM and to explore the possible mechanisms in relation to the p38 MAPK pathway.Forty rats were randomly divided into the following five groups (n = 8 each): a control + sham group, a control + IR group (CIR), a DM + sham group, a DM + IR group (DIR), and a DM + IR + SB203580 group. The control and streptozotocin-induced diabetic rats underwent a sham operation or left hilum occlusion for 90 min followed by reperfusion for 4 h. SB203580 was used to inhibit the p38 MAPK pathway. The pulmonary oxygenation index, inflammatory cytokines in the serum, lung edema, histopathology, oxidant stress, apoptosis, and phosphorylated/total-p38 MAPK protein levels were measured.The DIR group displayed greater concentrations of tumor necrosis factor-α, interleukin-6, and intercellular adhesion molecule-1 and increases in the wet weight-to-dry weight ratio, lung injury scores, malondialdehyde levels, and cellular apoptosis, and these effects were accompanied by lower pulmonary oxygenation compared with the CIR group (P 0.05). In the DIR group, the expression levels of p38 MAPK protein were significantly upregulated compared with those of the CIR group. Additionally, all of these alterations were attenuated in the DM + IR + SB203580 group compared with the DIR group.Diabetes exacerbates LIRI by activating the p38 MAPK pathway.

Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH2O for 4 h and randomly given FiCO2 to achieve normocapnia (PaCO2 at 35-45 mm Hg) or hypercapnia (PaCO2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH2O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways.

Background Hypoxia–reoxygenation of cultured macrovascular endothelial cells is used to study ischemia–reperfusion (IR)-related cellular and molecular changes; however, these models do not accurately depict events in pulmonary microvascular endothelial cells (PMVECs) during conventional lung retrieval and transplantation. We used rat PMVECs in a new non-hypoxic cell-based lung transplantation model to assess these events. Methods To simulate cold storage, rat PMVECs were preserved in 95% O 2 –5% CO 2 at 4°C for 6 hours in low-potassium dextran solution. Dishes were warmed for 1 hour to room temperature for simulating implantation. Medium was added at 37°C in 50% O 2 –5% CO 2 –45% N 2 to simulate reperfusion. Additional PMVECs were transfected with siRNA targeting mitogen-activated protein kinases (MAPKs) and then subjected to simulated IR. Results MAPKs and NF-κB were activated during simulated reperfusion, and AP-1 was activated during ischemia and reperfusion. Increased malondialdehyde levels were found during cold ischemia, and apoptosis and production of IL-1β, IL-6, and TNF-α were observed during reperfusion. Silencing of MAPKs attenuated oxidative stress, inflammation and apoptosis. Silencing of JNK and p38 decreased NF-κB phosphorylation and increased inhibitor of NF-κB (IκB)α levels. Knockdown of ERK1/2 increased NF-κB phosphorylation but had no effect on IκBα expression. Silencing of JNK and ERK1/2, but not p38, decreased AP-1 phosphorylation. Conclusions Exposing rat PMVECs to simulated non-hypoxic IR caused lipid peroxidation, inflammation and apoptosis, which required MAPK-mediated NF-κB and AP-1 activation and distinct regulation of MAPKs by these 2 transcription factors. This model could be used to uncouple mechanisms of IR and evaluate potential therapeutics in alleviating IR injury.

Background The process of brain death induces acute lung injury in donors and aggravates ischemia–reperfusion injury (IRI) in grafts. Hydrogen, a new anti-oxidant, attenuates IRI in several organ transplant models. We examined whether 2% inhaled hydrogen would show favorable effects on lung grafts from brain-dead donor rats. Methods Brain-dead donor rats inhaled mixed gases with either 50% oxygen and 50% nitrogen or mixed gases with 2% hydrogen, 50% oxygen and 48% nitrogen for 2 hours. The recipients inhaled the same gas as the donors and were euthanized 2 hours after lung transplantation. Results Hydrogen improved PaO 2 /FIO 2 and PVO 2 /FIO 2 from the arterial and pulmonary venous blood in recipients and decreased the lung injury score in grafts from brain-dead donors. Hydrogen decreased the amount of IL-8 and TNF-α in serum, inhibited the activity of malondialdehyde and myeloperoxidase, and increased the activity of superoxide dismutase in the lung grafts from brain-dead donors. Furthermore, hydrogen decreased the apoptotic index of the cells and inhibited the protein expression of intercellular adhesion molecule-1 and caspase-3 in lung grafts from brain-dead donors. Conclusions Hydrogen can exert protective effects on lung grafts from brain-dead donors through anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms.

Antioxidants induce the proliferation of cancers by decreasing the expression of p53. Propofol, one of the most extensively used intravenous anesthetics, provides its antioxidative activity via activation of the nuclear factor E2-related factor-2 (Nrf2) pathway, but the mechanisms involved in the effects remain unknown. Thus, we aimed to investigate the function of p53 and Nrf2 in the human breast cancer cell line MDA-MB-231 following treatment with propofol. The cells were treated with propofol (2, 5 and 10 µg/ml) for 1, 4 and 12 h, and MTT assay was used to evaluate cell proliferation, and a wound healing assay was used to evaluate cell migration. Cell apoptosis, caspase-3 activity, and western blot analysis for p53 and Nrf2 protein were also assessed. Finally, PIK-75, a potent Nrf2 inhibitor, was used to confirm the effects of Nrf2 after treatment with propofol. Treatment of MDA-MB‑231 cells with propofol resulted in increased proliferation and migration in a dose- and time-dependent manner. After treatment with propofol for 12 h, the Nrf2 protein expression was increased, while the percentage of apoptotic cells, caspase-3 activity, and expression of p53 were significantly decreased. Additionally, treatment with the Nrf2 inhibitor increased the percentage of apoptotic cells, inhibited the migration almost completely, and decreased the degree of proliferation, while the expression of p53 was not affected. In conclusion, propofol increased the proliferation of human breast cancer MDA-MB‑231 cells, which was at least partially associated with the inhibition of the expression of p53, and induced cell migration, which was involved in the activation of the Nrf2 pathway.

Gastrointestinal motility may be impaired after intestinal surgery. Epidural morphine is effective in controlling postoperative pain, but can further reduce gastrointestinal motility. Here, we aimed to investigate the effects of epidural dexmedetomidine on gastrointestinal motility in patients undergoing colonic resection. Seventy-four patients undergoing colonic resection were enrolled in this clinical trial and allocated randomly to treatment with dexmedetomidine (D group) or morphine (M group). The D group received a loading dose epidural administration of 3 ml dexmedetomidine (0.5 μg kg-1) and then a continuous epidural administration of 80 μg dexmedetomidine in 150 ml levobupivacaine (0.125%) at 3 ml h-1 for two days. The M group received a loading dose epidural administration of 3 ml morphine (0.03 mg kg-1) and then a continuous epidural administration of 4.5 mg morphine in 150 ml levobupivacaine at 3 ml h-1 for two days. Verbal rating score (VRS), postoperative analgesic requirements, side effects related to analgesia, the time to postoperative first flatus (FFL) and first feces (FFE) were recorded. VRS and postoperative analgesic requirements were not significantly different between treatment groups. In contrast, the time to FFL and time to FFE were significant longer in M group in comparison to D group (P < 0.05). Moreover, patients in M group had a significantly higher incidence of nausea, vomiting, and pruritus (P < 0.05). No patients showed neurologic deficits in either group. In comparison to morphine, epidural dexmedetomidine is safe and beneficial for the recovery of gastrointestinal motility after colonic resection when used as an adjunct with levobupivacaine for postoperative pain control. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-14004644

Background Lung ischemia–reperfusion injury (LIRI) remains a significant problem after lung transplantation. A crucial signaling enzyme involved in inflammation and apoptosis during LIRI is p38 mitogen-activated protein kinase (MAPK). Gene silencing of p38α by short hairpin RNA (shRNA) can downregulate p38α expression. The lungs have an extremely large surface area, which makes the absorption of shRNA highly effective. Therefore, we evaluated the therapeutic efficacy of p38α shRNA plasmids in a rat model of lung transplantation. Methods The delivery of p38α shRNA plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. Control animals received scrambled shRNA plasmids. Reverse-transcription polymerase chain reaction and Western blots were used to assess gene silencing efficacy. The therapeutic effects of shRNA plasmids were evaluated by lung function tests. We determined the levels of inflammatory cytokines, the level of intercellular adhesion molecule 1 (ICAM-1), c-Myc mRNA expression, and ICAM-1 protein expression, and the presence of cell apoptosis. Results Rats administered p38α shRNA plasmids showed a significant downregulation in lung expression of p38α transcripts and protein levels. Compared with the control group, the p38α shRNA group showed a higher pulmonary vein oxygen level, lower wet weight-to-dry weight ratio, lower lung injury score, and lower serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-8. Messenger RNA levels of ICAM-1 and c-Myc in the p38α shRNA group were dramatically lower than in the control group. Levels of ICAM-1 protein expression exhibited a similar trend. Cell apoptosis decreased in the p38α shRNA group vs the control group. Conclusion Intratracheal administration of p38α shRNA plasmids provided therapeutic effects in a rat model of lung transplantation.

Lung ischemia-reperfusion injury (IRI) may be attenuated through carbon monoxide (CO)'s anti-inflammatory effect or hydrogen (H2)'s anti-oxidant effect. In this study, the effects of lung inflation with CO, H2, or both during the cold ischemia phase on graft function were observed.Rat donor lungs, inflated with 40% oxygen (control group), 500ppm CO (CO group), 3% H2 (H2 group) or 500ppm CO+3% H2 (COH group), were kept at 4°C for 180min. After transplantation, the recipients' artery blood gas and pressure-volume (P-V) curves were analyzed. The inflammatory response, oxidative stress and apoptosis in the recipients were assessed at 180min after reperfusion.Oxygenation in the CO and H2 groups were improved compared with the control group. The CO and H2 groups also exhibited significantly improved P-V curves, reduced lung injury, and decreased inflammatory response, malonaldehyde content, and cell apoptosis in the grafts. Furthermore, the COH group experienced enhanced improvements in oxygenation, P-V curves, inflammatory response, lipid peroxidation, and graft apoptosis compared to the CO and H2 groups.Lung inflation with CO or H2 protected against IRI via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms in a model of lung transplantation in rats, which was enhanced by combined treatment with CO and H2.

Background Permissive hypercapnia is a widely practiced protective ventilatory strategy that has significant protective effects on several models of in vitro and in vivo neuronal injury. However, conclusive effects of permissive hypercapnia on cerebral ischemia are still unknown. Methods One hundred sixty male Wistar rats were divided into five groups: S group (control), ischemia-reperfusion (I/R) group, P1 group, P2 group, and P3 group. I/R was induced by bilateral occlusion of the common carotid arteries, combined with controlled hypotension for 15 min. In groups P1, P2, and P3, the rats inhaled carbon dioxide for 2 h during reperfusion to keep Paco2 within the ranges of 60-80 mmHg, 80-100 mmHg, and 100-120 mmHg, respectively. After 24 and 72 h, neurologic deficit scores, ultrastructural changes, apoptotic neurons, and brain wet-to-dry weight ratios were observed. Caspase-3 and aquaporin-4 protein expression and caspase-3 activity were analyzed. Results Compared with groups I/R and P3, groups P1 and P2 had better neurologic deficit scores and fewer ultrastructural histopathologic changes. I/R-induced cerebral apoptosis was also significantly reduced. The neuroprotective effect was significantly increased in the P2 group compared with the P1 group. There was a significant increase of brain water content and of aquaporin-4 levels in the P3 group. Conclusions Mild to moderate hypercapnia (Paco2 60-100 mmHg) is neuroprotective after transient global cerebral I/R injury. Such a protection might be associated with apoptosis-regulating proteins. In contrast, severe hypercapnia (Paco2 100-120 mmHg) increased brain injury, which may be caused by increased brain edema.

Background Heme oxygenase 1 (HO-1) has been shown to attenuate neuronal injury. Therefore, the authors examined whether HO-1 would reduce the brain damage caused by cardiac arrest. Methods Rats anesthetized with halothane were subjected to 8 min of cardiac arrest by asphyxia without any pretreatment (control group) or pretreated with an inducer of HO-1 (hemin group) or with an inhibitor of HO-1 (tin protoporphyrin group). Then, the animals were resuscitated with a standardized method. Brain water content (1 and 6 h after resuscitation), neurologic deficit score, viable neuronal counts, and caspase-3 immunostaining in the hippocampus (4 and 14 days) were evaluated. Results Water content in the hemin group was significantly reduced (mean +/- SD: 83.1 +/- 1.9% for 1 h after resuscitation; P = 0.03) and significantly greater in the tin protoporphyrin group (91.1 +/- 2.0% for 1 h after resuscitation; P = 0.035) when compared with the control group (88.2 +/- 2.4%). Water content of the cortex was nearly the same as that of the hippocampus. Neurologic deficit scores and neuronal survival were significantly better in the hemin group than in the control group on the 4th and 14th days. In rats that survived for 4 days, the amount of caspase 3-positive neurons was 27 +/- 7 in the control group, whereas the value was 14 +/- 6 in the hemin group (P < 0.05). Conclusions In rats resuscitated from cardiac arrest, induction of HO-1 by hemin reduced brain edema, improved neurologic outcome, and protected neurons against apoptosis.

Background We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 “doses” (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. Methods Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. Results In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p

Opioids produce delayed pre-conditioning (PC) in vivo and in vitro. Our previous research revealed that opioid‑induced delayed PC has an antiapoptotic effect on pulmonary artery endothelial cells (PAECs) suffering from anoxia/reoxygenation (A/R) injury. The present study hypothesized that activation of endothelial mitochondrial ATP‑sensitive potassium (KATP) channels may result in antiapoptotic effects and against dysfunction in PAECs. Cultured porcine PAECs underwent 16 h anoxia treatment, followed by 1 h reoxygenation, which occurred 24 h following pretreatment with saline (0.9% NaCl; w/v) or morphine (1 µM). To determine the underlying mechanism, a selective mitochondrial KATP inhibitor, 5‑hydroxydecanoic acid (5‑HD; 100 µM), and an opioid receptor antagonist, naloxone (Nal; 10 µM), were administered 30 min prior to the A/R load. The percentage of apoptotic cells was assessed by Annexin V‑fluorescein isothiocyanate staining, using a fluorescence‑activated cell sorter. The mRNA expression of intercellular cell adhesion molecule‑1 (ICAM‑1) was measured by reverse transcription‑quantitative polymerase chain reaction. The endothelin‑1 (ET‑1) content in the supernatant of PAECs cultures was estimated by radioimmunoassay. Compared with the control, A/R caused the apoptosis of PAECs, release of ET‑1 and increased mRNA expression of ICAM‑1. Morphine‑induced delayed PC significantly reduced PAEC apoptosis, increased the release of ET‑1 and reduced the mRNA expression of ICAM‑1 by ~1.7‑times, compared with A/R. The protective effect of morphine was abolished by pretreatment with 5‑HD and Nal, however, the two agents themselves failed to aggravate the A/R injury. These results suggested that morphine-induced delayed PC has a protective effect during A/R injury of PAECs. This effect may be mediated by mitochondrial KATP channels and is opioid receptor-dependent.

In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50–75 mg kg–1) through the airways. When the PaO2 had decreased to –1, 20 ml kg–1), whereas G 1–5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg–1), and G 3 and 8 received Curosurf (100 mg kg–1) plus dextran (75 mg kg–1); G 4 and 9 received Curosurf (200 mg kg–1), and G 5 and G 10 received Curosurf (200 mg kg–1) plus dextran (75 mg kg–1). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO2 transiently increased to 30–40 kPa. In G 4, 5, 9, and 10, the PaO2 remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg–1) was nevertheless required to optimize gas exchange.

This paper presents a novel low-rank and sparse decomposition (LSD) based model for anomaly detection in hyperspectral images. In our model, a local image region is represented as a low-rank matrix plus spares noises in the spectral space, where the background can be explained by the low-rank matrix, and the anomalies are indicated by the sparse noises. The detection of anomalies in local image regions is formulated as a constrained LSD problem, which can be solved efficiently and robustly with a modified “Go Decomposition” (GoDec) method. To enhance the validity of this model, we adapts a “simple linear iterative clustering” (SLIC) superpixel algorithm to efficiently generate homogeneous local image regions i.e. superpixels in hyperspectral imagery, thus ensures that the background in local image regions satisfies the condition of low-rank. Experimental results on real hyperspectral data demonstrate that, compared with several known local detectors including RX detector, kernel RX detector, and SVDD detector, the proposed model can comfortably achieves better performance in satisfactory computation time.

This paper proposes a novel top-down visual saliency detection method for optical satellite images using local adaptive regression kernels. This method provides a saliency map by measuring the likeness of image patches to a given single template image. The local adaptive regression kernel (LARK) is used as a descriptor to extract feature and compare against analogous feature from the target image. A multi-scale pyramid of the target image is constructed to cope with large-scale variations. In addition, accounting for rotation variations, the histogram of kernel orientation is employed to estimate the rotation angle of image patch, and then comparison is performed after rotating the patch by the estimated angle. Moreover, we use the bounded partial correlation (BPC) to compare features between image patches and the template so as to rapidly generate the saliency map. Experiments were performed in optical satellite images to find airplanes, and experimental results demonstrate that the proposed method is effective and robust in complex scenes.

In the monomeric dinuclear title complex, [CuSm(C(20)H(22)N(2)O(4))(NO(3))(3)], the four-coordinate Cu(II) ion has a square-planar geometry involving two O atoms and two N atoms of the deprotonated Schiff base ligand. The Sm(III) ion is ten-coordinate, chelated by four O donor atoms of the Schiff base and two O atoms each from three bidentate nitrate groups, one of which is disordered over two sites in a 0.55 (7):0.45 (7) ratio.

Introduction: To investigate the changes in coagulation function and component transfusion time in patients with massive hemorrhage. Methods: Sixty-two patients with massive hemorrhage were enrolled in the study. Blood samples were collected from each patient when the blood loss reached 1000, 1500, 1700 and 2000 ml. The parameters FIB, PT, APTT, HGB, HCT, PLT and MAP were recorded for all patients. Results: Sixty-two, 30, 20 and 8 patients showed blood loss exceeding 1000, 1500, 1700 and 2000 ml, respectively. Blood samples were successfully collected from all patients when the volume of blood lost reached 1000, 1500, 1700 and 2000 ml. However, at this time point, FIB, MAP, HGB, HCT and PLT were significantly lower than the baseline/preoperative values. These indices decreased progressively with increasing blood loss. PT and APTT were significantly higher than at baseline and increased progressively with increased blood loss. FIB, HCT and HGB were below the normal reference range when blood loss was 1500 ml. During surgery, FIB, MAP, HCT, HGB and PLT decreased substantially, whereas APTT and PT increased when blood loss exceeded 1500 ml. PT and MAP were beyond the normal range when blood loss reached 2000 ml. There was a correlation between FIB, HCT and HGB with intraoperative blood loss; the correlation coefficient was greatest between and FIB and blood loss. Conclusion: There were marked correlations between FIB, HCT and HGB with intraoperative blood loss, and the correlation was greatest with FIB.

Surfactant therapy for acute respiratory distress syndrome (ARDS) has shown encouraging results in animal studies, but not always in clinical trials. Efficacy of this therapy may be limited to ARDS caused by indirect injury, but mistiming of its application in clinical trials may be responsible for the discouraging results. In addition, the therapy may not last long enough to be effective. In rats with acidified milk aspiration, the effects of aerosolized surfactant therapy followed by inhalation of aerosolized dextran (molecular weight, 40,000) last significantly longer than those of aerosolized surfactant therapy alone. This mode of surfactant therapy could lead to better results since it can be started and repeated at any time.

The traditional smoothing and denoising method of point clouds usually needs to establish topological relations among points to go through their K-nearest neighbors in the three-dimensional reconstruction based on phase-measuring profilometry, which has brought about the dramatic increase in computational complexity. A new algorithm of denoising algorithms of phase diagram was put forward to eliminate scatterplots dislodging of the point clouds with high speed to decrease computational complexity greatly. Some Image smooth filtering algorithm were also applied to phase diagram to make the point clouds be more smoother. The experimental results show that the proposed algorithm can improve the quality of point clouds of 1.3 million point clouds only within 4 seconds on current PC.

Background: Overdistension of the lungs is a cause of ventilator-induced lung injury. In meconium aspiration syndrome, irregular overdistension of the lungs often occurs. Objectives: We investigated whether surfactant replacement could restore the terminal airspaces in the lungs that had been distended after meconium aspiration. Methods: Meconium aspiration was induced by injecting meconium (50 mg·kg–1) into the airways of adult rats anesthetized with pentobarbital and ventilated with pressure-preset mode. The animals were further ventilated with or without surfactant replacement (100 mg·kg–1), and the sizes of the terminal airspaces were determined after fixing the lungs at an airway pressure of 10 cm H2O on deflation. Results: Approximately 75 min after aspiration (early analysis point), alveolar ducts were widened and the mean ratio of the largest terminal airspace size class (≧63,000 µm2) was 38.7% (n = 7), which was significantly higher than that of controls (6%, n = 7). Three hours after the early analysis point, the ratio increased to 50.2% (n = 7, p < 0.05), but surfactant replacement reversed the ratio to 18.8% (n = 7, p < 0.05). Conclusions: In rats with meconium aspiration, surfactant replacement restored the distended terminal airspaces of the lungs and kept the spaces from irregular overdistension.

In acute respiratory distress syndrome, mechanical ventilation often induces alveolar overdistension aggravating the primary insult. To examine the mechanism of overdistension, surfactant-deficient immature rabbits were anesthetized with pentobarbital sodium, and their lungs were treated with serum-diluted modified natural surfactant (porcine lung extract; 2 mg/ml, 10 ml/kg). By mechanical ventilation with a peak inspiration pressure of 22.5 cmH2O, the animals had a tidal volume of 14.7 ml/kg (mean), when 2.5 cmH2O positive end-expiratory pressure was added. This volume was similar to that in animals treated with nondiluted modified natural surfactant (24 mg/ml in Ringer solution, 10 ml/kg). However, the lungs fixed at 10 cmH2O on the deflation limbs of the pressure-volume curve had the largest alveolar/alveolar duct profiles (≥48,000 μm2), accounting for 38% of the terminal air spaces, and the smallest (2), accounting for 31%. These values were higher than those in animals treated with nondiluted modified natural surfactant ( P < 0.05). We conclude that administration of serum-diluted surfactant to immature neonatal lungs leads to patchy overdistension of terminal air spaces, similar to the expansion pattern that may be seen after dilution of endogenous surfactant with proteinaceous edema fluid in acute respiratory distress syndrome.

Surfactant protein (SP)-C is characterized by α-helix structure and palmitoyl groups attached to two cysteine residues. We examined the function of palmitoylation and dimerization in promotion of tidal volume in immature newborn rabbits. Reconstituted surfactants were made from a mixture of synthetic phospholipids and porcine SP-B (basic mixture) by adding various forms of SP-Cs: normal SP-C isolated from porcine lungs and monomeric or dimeric forms of SP-C. These latter two were isolated from patients with pulmonary alveolar proteinosis and were less palmitoylated. Animals were ventilated at an inspiratory pressure of 25 cmH2O. Median tidal volumes were 18 ml/kg in animals treated with reconstituted surfactants containing 3% normal or 2% dimeric SP-C ( P < 0.05 vs. basic mixture). The physiological effect of basic mixture was not improved by monomeric SP-C. We conclude that palmitoyl groups are important for the physiological effects of SP-C and that the dimeric form also improves physiological effects.