Functional analysis of UDP-glycosyltransferase genes conferring indoxacarb resistance in Spodoptera litura.

UDP-glycosyltransferase (UGT) is the major detoxification enzymes of phase II involved in xenobiotics metabolism, which potentially mediates the formation of insect resistance. Previous transcriptome sequencing studies have found that several UGT genes were upregulated in indoxacarb resistant strains of Spodoptera litura, but whether these UGT genes were involved in indoxacarb resistance and their functions in resistance were unclear. In this study, the UGTs inhibitor, 5-nitrouracil, enhanced the toxicity of indoxacarb against S. litura, preliminarily suggesting that UGTs were participated in indoxacarb resistance. Two UGT genes, UGT33J17 and UGT41D10 were upregulated in the resistant strains and could be induced by indoxacarb. Alignment of UGT protein sequences revealed two conserved donor-binding regions with several key residues that interact with catalytic sites and sugar donors. Further molecular modeling and docking analysis indicated that two UGT proteins were able to stably bind indoxacarb and N-decarbomethoxylated metabolite (DCJW). Furthermore, knockdown of UGT33J17 and UGT41D10 decreased viability of Spli-221 cells and enhanced susceptibility of larvae to indoxacarb. Transgenic overexpression of these genes reduced the toxicity of indoxacarb in Drosophila melanogaster. This work revealed that upregulation of UGT genes significantly contributes to indoxacarb resistance in S. litura, and is of great significance for the development of integrated and sustainable management strategies for resistant pests in the field.

Transdermal Photothermal Sterilization and Abscess Elimination Research of BSA-CuS Nanoparticles in vivo.

The treatment of subcutaneous abscess caused by drug-resistant bacteria is facing great difficulties and receiving more attention. In this work, we employed BSA-CuS nanoparticles as a photothermal reagent to apply photothermal therapy (PTT) to combat drug-resistant bacteria in vitro and subcutaneous abscess in vivo. The BSA-CuS nanoparticles were found to be stable and biocompatible without cytotoxicity toward NIH3T3 and 4T1 cells. In vitro experiments showed that three species of drug-resistant pathogens, including Escherichia coli, Staphylococcus aureus, and Candida albicans, could be effectively sterilized under co-incubation with BSA-CuS nanoparticles and then irradiation with 1064 nm NIR laser via tissue penetration. BSA-CuS nanoparticles together with 1064 nm NIR laser irradiation could also effectively diminish subcutaneous abscesses caused by drug-resistant bacteria on mice under PTT and depth PTT without causing any serious side effects and organic damage in vivo.That is OK, thank you!

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis.

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber-Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

Efficiency of Monocyte/High-Density Lipoprotein Cholesterol Ratio Combined With Neutrophil/Lymphocyte Ratio in Predicting 28-Day Mortality in Patients With Sepsis.

Background: Sepsis can cause unpredictable harm, and early identification of risk for mortality may be conducive to clinical diagnosis. The present study proposes to assess the efficacy of the monocyte/high-density lipoprotein cholesterol ratio (MHR) combined with the neutrophil/lymphocyte ratio (NLR) on the day of admission in predictive efficacy in the 28-day mortality risk in critical patients with sepsis. Material and Methods: We administered observational and retrospective cohort research from a single center. The correlation of the clinical variables, together with the system severity scores of APACHE II and SOFA, are displayed by correlation analysis, and a Cox regression model could be performed to screen the independent risk factors and estimate the capacity of multiple markers in predicting 28-day mortality. The receiver operating characteristic (ROC) curve served as an applied method to output cutoff values for the diagnosis and prognostic risk, and the area under the ROC curve and net reclassification improvement index (NRI), as well as integrated discrimination improvement index (IDI) were employed to assess the feasibility of multiple parameters for predictive value in 28-day mortality of septic patients. Results: The study enrolled 274 eligible patients with sepsis. The correlation analysis indicated NLR and MHR were related to the sepsis severity. A multivariate Cox regression analysis indicated that NLR together with MHR displayed a close relation to death rate after adjusting for other potential confounders (NLR, HR = 1.404 [95% CI 1.170-1.684], P < 0.001; MHR, HR = 1.217 [95% CI 1.112-1.331], P < 0.001). The AUC of NLR, MHR, NLR_MHR was 0.827, 0.876, and 0.934, respectively. The addition on the biomarker NLR_MHR to the prediction model improved IDI by 18.5% and NRI by 37.8%. Conclusions: Our findings suggest that NLR and MHR trend to an elevated level in non-surviving patients with sepsis. Evaluation of NLR_MHR, an independent risk factor for increased mortality, might improve the predictive efficacy for 28-day mortality risk in septic patients.

TNF-α-induced protein 8-like 2 negatively regulates the immune function of dendritic cells by suppressing autophagy via the TAK1/JNK pathway in septic mice.

Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-ß (TGF-ß)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation.

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.

Growth and Development of Helicoverpa armigera (Lepidoptera: Noctuidae) Larvae Infected by Heliothis virescens ascovirus 3i (HvAV-3i).

Although the cotton bollworm Helicoverpa armigera has traditionally been controlled by application of chemical pesticides, chemical control selects for resistance, pollutes the environment, and endangers human health. New methods for controlling H. armigera are therefore needed. Heliothis virescens ascovirus 3i (HvAV-3i) is a recently identified virus of the lepidopteran larvae. We tested the effects of HvAV-3i on H. armigera larvae following oral ingestion of HvAV-3i-containing hemolymph (about 1.0 × 1010 virus genome copies per larvae) and following injection of HvAV-3i-containing hemolymph by insertion of a needle. Following oral ingestion, first-instar to fifth-instar larvae grew and developed normally. Following needle injection, in contrast, the corrected mortality of third and fourth instars was 88.9 ± 2.1 and 93.7 ± 3.4%, respectively. Food intake was significantly lower for larvae injected with virus-containing hemolymph than with virus-free hemolymph. Larvae injected with virus-containing hemolymph had extended survival times and could not complete the pre-pupal stage. These results indicate that inoculation of HvAV-3i via needle injection, but not via oral ingestion, significantly reduced the growth and development of H. armigera larvae.

Regulation of Chitinase in Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) During Infection by Heliothis virescens ascovirus 3h (HvAV-3h).

Insect chitinases play essential roles in the molting and metamorphosis of insects. The virus Heliothis virescens ascovirus 3h (HvAV-3h) can prolong the total duration of the larval stage in its host larvae. In this study, the molecular character and function of chitinase and chitin-binding domain (CBD) were analyzed in larvae of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae). In detecting the chitinase activity of mock-infected and HvAV-3h-infected larval whole bodies and four different larval tissues, the results showed that larval chitinase activity was significantly decreased at 48 h post infection (hpi) and that the chitinase activity of HvAV-3h-infected larval fat body and cuticle was notably decreased at 144 and 168 hpi. The transcription level of S. exigua chitinase 7 (SeCHIT7) was down-regulated at the 6, 9, 12, 48, 72, and 96 hpi sample times, the S. exigua chitinase 11 (SeCHIT11) was down-regulated at 3-96 hpi, while both S. exigua chitinases (SeCHITs) were up-regulated at 120-168 hpi. Further tissue-specific detection of SeCHIT7 and SeCHIT11 transcription showed that SeCHIT7 was down-regulated at 144 and 168 hpi in the fat body and cuticle. SeCHIT11 was down-regulated at 168 hpi in the fat body, midgut, and cuticle. Additionally, the transcription and expression of S. exigua chitin-binding domain (SeCBD) could not be detected in HvAV-3h-infected larvae. The in vitro analyses of SeCHIT7N, SeCHIT11, and SeCBD showed that SeCHIT7N and SeCHIT11 were typical chitinases. Conversely, no chitinase activity was detected with SeCBD. SeCBD, however, could significantly increase the activity of SeCHIT7N and SeCHIT11. In conclusion, HvAV-3h not only interfered with the transcription and expression of SeCHITs but also affected the normal transcription and expression of SeCBD and, in doing so, influenced the host larval chitinase activity. These results will aid in providing a foundation for further studies on the pathogenesis of HvAV-3h.

A CNN-Based Method for Intent Recognition Using Inertial Measurement Units and Intelligent Lower Limb Prosthesis.

Powered intelligent lower limb prosthesis can actuate the knee and ankle joints, allowing transfemoral amputees to perform seamless transitions between locomotion states with the help of an intent recognition system. However, prior intent recognition studies often installed multiple sensors on the prosthesis, and they employed machine learning techniques to analyze time-series data with empirical features. We alternatively propose a novel method for training an intent recognition system that provides natural transitions between level walk, stair ascent / descent, and ramp ascent / descent. Since the transition between two neighboring states is driven by motion intent, we aim to explore the mapping between the motion state of a healthy leg and an amputee's motion intent before the upcoming transition of the prosthesis. We use inertial measurement units (IMUs) and put them on the healthy leg of lower limb amputees for monitoring its locomotion state. We analyze IMU data within the early swing phase of the healthy leg, and feed data into a convolutional neural network (CNN) to learn the feature mapping without expert participation. The proposed method can predict the motion intent of both unilateral amputees and the able-bodied, and help to adaptively calibrate the control strategy for actuating powered intelligent prosthesis in advance. The experimental results show that the recognition accuracy can reach a high level (94.15% for the able-bodied, 89.23% for amputees) on 13 classes of motion intent, containing five steady states on different terrains as well as eight transitional states among the steady states.

The complete mitochondrial genome of Bombyx lemeepauli (Lepidoptera: Bombycidae) and its phylogenetic relationship.

The complete mitochondrial genome (mitogenome) of Bombyx lemmepauli Lemée has been sequenced with 15,801 bp in length (Genbank no. KY620270), and has a base composition of A (43.17%), G (7.40%), C (11.90%), and T (37.86%). Similar to other bombyciod species, it contains a typically conserved structure including 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and an A + T-rich region. Excepting cox1 started with CGA, the start codons of the other 12 PCGs were ATN. Eleven of the 13 PCGs ended with TAA, expect for cox1 and cox2, which ended with a single T. The complete mitogenome sequence provided here would be useful for further understanding the evolutional position of B. lemeepauli, which is a key species to relate the famous resource insect B. mori and the important insect pest Rondotia menciana (Lepidoptera: Bombycidae).

AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells.

A meta-analysis of the success rates of heartbeat restoration within the platinum 10 min among outpatients suffering from sudden cardiac arrest in China.

BACKGROUND: The optimal time to save a person who has had a sudden cardiac arrest is within the first few minutes of the incident. Early compression and early defibrillation should be performed at this time. Timeliness is the key to successful CPR; as such, Prof. He proposed the "platinum 10 min" system to study early CPR issues. This paper systematically evaluates the success rates of heartbeat restoration within the "platinum 10 min" among patients suffering from sudden cardiac arrest. METHODS: The clinical data of outpatients suffering from a cardiac arrest were retrieved from the China Knowledge Network (January 1975-January 2015), the Chongqing VIP database (January 1989-January 2015), and the Wanfang database (January 1990-January 2015). The success of the cardiopulmonary resuscitation (CPR) performed at different times after the patients had cardiac arrests was analyzed. Two researchers screened the literature and extracted the data independently. A meta-analysis was conducted using Stata12.0. A total of 57 papers met the inclusion criteria, including 29,269 patients. Of these patients, 1776 had their heartbeats successfully restored. The results showed high heterogeneity (X (2) = 3428.85, P < 0.01, I(2) = 98.4 %). The meta-analysis was conducted using a random-effects model. The combined effect size was 0.171 (0.144-0.199). RESULTS: (1) The success rate of heartbeat restoration did not differ among the four emergency treatment methods that patients received: the methods described in the 2000 Guidelines for CPR and Emergency Cardiovascular Care, that described in the 2005 version, 2010 version, and another CPR method. (2) The patients were divided into five groups based on the time when CPR was performed: the ≤1 min group, the 1- ≤ 5 min group, the 5- ≤ 10 min group, the 10- ≤ 15 min group and the >15 min group. The CPR success rates of these five groups were 0.247 (0.15-0.344), 0.353 (0.250-0.456), 0.136 (0.109-0.163), 0.058 (0.041-0.075), and 0.011 (0.004-0.019), respectively. The CPR success rates did not differ between the patients in the ≤1 min group and the 1- ≤ 5 min group. This success rate was higher for the patients in the 1- ≤ 5 min group than those in the 10- ≤ 15 min group, those in the 10- ≤ 15 min group, and those in the >15 min group. The CPR success rate was higher for the patients in the 5-10 min group than those in the 10- ≤ 15 min group and those in the >15 min group. CONCLUSIONS: The CPR success rate was higher for the patients in the 10- ≤ 15 min group than those in the >15 min group. In addition, the patients were divided into two groups based on whether CPR was performed within the first 10 min after the cardiac arrest occurred: the ≤10 min group and the >10 min group. The CPR success rate was higher for the patients in the ≤10 min group (0.189 [0.161-0.218]) than those in the >10 min group (0.044 [0.032-0.056]). (3) Differences were not found between the CPR success rates among the patients in the telephone guidance group (0.167 [0.016-0.351]) and those in the ≤1 min, 1- ≤ 5 min, 5- ≤ 10 min, 10- ≤ 15 min, and >15 min groups. (4) The CPR success rates did not differ among in the patients in the witness + public group (0.329 [0.221-0.436]), those in the ≤1 min group, and those in the 1- ≤ 5 min group. However, this success rate was higher in the patients in the witness + public group than those in the 5- ≤ 10 min, 10- ≤ 15 min, and >15 min groups. CONCLUSIONS: The success rate of heartbeat restoration did not differ among patients receiving CPR based on different guidelines. The success rate of CPR lies in its timeliness. The participation of the general population is the cornerstone of improving CPR. Providing complete emergency treatment equipment and perfecting comprehensive measures can improve the success rate of CPR among patients within the platinum 10 min. CPR research in China must be improved.

[Mechanisms of the role of fibroblast growth factor 21 in attenuating insulin resistance].

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 µmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.

Anticoagulant effect of Huisheng Oral Solution in a rat model of thrombosis.

OBJECTIVE: To investigate whether Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis. MATERIALS AND METHODS: A total of 40 male SD rats were equally and randomly divided into four groups: blank group, model group, and two treatment groups (A and B). Rats were subcutaneously injected with carrageenan to induce thrombosis. Rats in the treatment group A were intragastrically administered with Huisheng Oral Solution at a dose of 2 ml/100 g body weight (once per 8 hours), 72 hours after carrageenan injection, while those in the treatment group B were administered with Huisheng Oral Solution both 72 hours before and after induction of thrombosis. Blood samples were collected 24, 48, and 72 hours after carrageenan injection for measurements of prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB), prothrombin activity (PTA), platelets (PLT), fibrin degradation products (FDPs), and D-dimer. Lung, liver, and mesentery samples were taken 72 hours after carrageenan injection for histopathological analysis. The numbers of microthrombi in sections of different tissue samples were counted under a microscope. Blood parameters among each group were compared using the Welch test, the Kruskal-Wallis test, or the SNK test after testing for normality, while the number of microthrombi was compared using the Bonferroni test. RESULTS: Compared to those in the model group, PT, APTT, and INR were significantly prolonged or increased while FIB was significantly reduced at the majority of time points in the two treatment groups (P < 0.05 for all). The levels of FDPs and D-dimer and PLT counts at the majority of time points were significantly lower (P < 0.05 for all), and the numbers of microthrombi in lung, liver, and mesentery samples were significantly decreased (P < 0.05 for all) in the two treatment groups. The above parameters at the majority of time points showed no significant differences between the two treatment groups. CONCLUSIONS: Huisheng Oral Solution can significantly improve coagulation parameters, fibrinolysis parameters, and PLT count, and reduce blood hypercoagulability and microthrombosis, suggesting that Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis.

[Sedation with stimulative circadian rhythm in mechanically ventilation patients in intensive care unit].

OBJECTIVE: To sedate the mechanically ventilation patients in intensive care unit (ICU) with stimulative circadian rhythm, and evaluate whether the protocol has advantages in recovering natural circadian rhythm, duration of mechanical ventilation, and length of ICU stay after weaning of sedation. METHODS: A prospective random control trial was conducted. One hundred and twenty ventilated patients in ICU were randomly assigned to four groups: circadian rhythm (CR), daily interruption (DI), continuous sedation (CS) or demand sedation (DS) group, each n = 30. Given more complications, DS group was deleted after recruiting 10 cases and 90 patients were admitted ultimately. Patients' age, gender, body weight, acute physiology and chronic health evaluation II (APACHE II) scores, sedatives dosages, daily arousal time, duration of mechanical ventilation, length of ICU stay, complications (ventilator-associated pneumonia, barotrauma with intrathoracic drain tube) and untoward reactions (accidental extubation, reintubation, tracheotomy, death) were recorded, the biochemical indicators were determined, as well as number of nurses on duty at 10:00 and 22:00. RESULTS: The patients' sex ratio, age, body weight, APACHEII scores, duration of mechanical ventilation, length of ICU stay showed no difference among CR, DI and CS groups. The total sedatives dosages (mg: 5466.7 ± 620.4) and average sedatives dosages [mg×h(-1) ×kg(-1): 2.19 ± 0.61] in CS group were significantly higher than those in CR group (4344.5 ± 816.0, 1.00 ± 0.51) and DI group (4154.3 ± 649.4, 1.23 ± 0.62, all P < 0.01), and there was no difference between CR group and DI group. Daily arousal time in the CR group (hours: 4.40 ± 1.30) was significantly lengthened compared with that in DI group (0.59 ± 0.26) and CS group (0.15 ± 0.02, both P < 0.05). The complications showed no differences in each group, but incidences of the untoward reactions in DI group (2 cases) were significantly increased compared with that in CR group (1 case) and CS group (0 case, P = 0.0477). After weaning of sedation, patients with normal circadian rhythm were significantly more in CR group than that in CS group (19 vs. 9, P = 0.0339). Among CR group, DI group and CS group, there were significant differences in the numbers of nurses on duty in the daytime (1.65, 1.41, 1.14, all P < 0.01), but there was no difference in the night. The biochemistry index showed no difference in each group. CONCLUSIONS: It demonstrated that sedation with stimulative circadian rhythm be helpful to create circadian rhythm after weaning of sedation. While complications and untoward reactions did not increase, as well as duration of mechanical ventilation and length of ICU stay. Therefore, the clinical applicability of this sedative strategy was highlighted.

Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury.

Impaired lung function is the primary contributor to most deaths associated with severe acute pancreatitis. It is widely accepted that oxidative stress plays a central role in the pathogenesis of pancreatitis and associated complications. Therefore, in the present study, we investigated whether therapeutic treatment with the free radical scavenger edaravone could protect rats against acute pancreatitis and the associated lung injury. Acute pancreatitis was induced by infusion of 1ml/kg of sodium taurocholate (3% solution) into the biliopancreatic duct. Edaravone (8mg/kg) was administered 1h and 13h after inducing pancreatitis, the severity of pancreatic and pulmonary injuries was evaluated 24h after inducing pancreatitis. Edaravone treatment significantly reduced the elevated malondialdehyde levels in rat lungs after acute pancreatitis, suggesting an important role for free radicals in acute pancreatitis-associated lung injury. In addition, edaravone showed significant protective effects against neutrophil infiltration and tissue injury in both pancreas and lung, as demonstrated by serum amylase levels, myeloperoxidase activity and histopathological analysis. Edaravone treatment also attenuated the elevated mRNA levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in rat lungs after acute pancreatitis. In conclusion, edaravone protects rats against acute pancreatitis-associated lung injury, probably through its antioxidant and anti-inflammatory effects. Thus, edaravone shows promise as a treatment for lung injury in patients with acute pancreatitis.