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Background: Equipoise exists regarding the implementation of evidence-based guidelines for nutritional therapy in critical illness because some previous cluster-randomised controlled trials (cRCTs) demonstrate patient benefits whilst others do not. We aimed to resolve this issue by initiating an appropriately powered cRCT to assess whether active implementation of an evidence-based guideline for nutrition therapy in critical illness could reduce mortality. Methods: We did a multicentre, cluster-randomised, parallel-controlled trial in 97 intensive care units (ICUs) throughout China. We developed an up-to-date, evidence-based nutrition guideline. ICUs randomly allocated to implement the guideline formed a local "intervention team", which actively implemented the guideline using standardized educational materials. ICUs assigned to the control group remained unaware of the guideline. All ICUs enroled critically ill patients who were expected to stay longer than seven days. The primary outcome was all-cause mortality within 28 days of enrolment . Findings Between March, 2018 and July, 2019, we enrolled 1,373 patients at 48 guideline ICUs and 1,399 patients at 49 control ICUs. Implementation of the nutrition guideline resulted in significantly earlier enteral nutrition (EN) initiation (1.20 vs. 1.55 mean days to initiation of EN; difference -0.40 [95% CI, -0.71 to -0.09]; P=0.01) and delayed parenteral nutrition (PN) initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI, 0.44 to 1.67]; P=0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference -1.6% [95% CI -4.3% to 1.2%]; p=0.42) between study groups. Interpretation: Active implementation of an evidence-based guideline can change practice. Our active implementation strategy improved the provision of nutrition therapy to critically ill patients. However, in our cRCT, this improvement in care did not translate to a reduction in mortality. We did not identify any safety concerns associated with the active implementation of our evidence-based guideline for nutrition therapy. Trial Registration: The study was registered in the ISRCTN registry before enrolment commenced (No. ISRCTN12233792). Funding Statement: The study was funded by the Key Research and Development Program Foundation of Jiangsu Province of China (no. BE2015685) and Nutricia, Wuxi, China. Declaration of Interests: Dr. GSD reported receiving academic research grants related to nutrition in critical illness from the Australian National Health and Medical Research Council, Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd and speakers honoraria from Fresenius Kabi Deutschland GmbH, Baxter Healthcare Australia, Pty Ltd, Nestle Healthcare, Vevy, Switzerland and Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. Dr. AvZ reports personal fees from Baxter, personal fees from Nestle, personal fees from Fresenius Kabi, grants and personal fees from Nutricia, grants from Cardinal Health grants from Mermaid grants from Lyric, outside the submitted work. Dr. WqL reported receiving speakers honoraria from Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. No other disclosures were reported. Ethics Approval Statement: The study was approved by the local hospital ethics committees of all the participating ICUs. At each site, informed consent was obtained from the patients or their next of kin before enrolment.

Based on the three dimensional seismic data and drilling data in Gaoshiti–Moxi area, the structural characteristics and evolution process of strike-slip faults in the study area and their significance for gas accumulation were examined using the method of fault structure analysis. The results show that: (1) Transtensional strike-slip faults are developed in the Paleozoic in study area. On the profile, there are three types of structural styles: steep and erect, flower structures, “Y” and reversed “Y” type faults. On the plane, strike-slip faults developed in the Cambrian extending linearly and along the nearly EW, NW and NE direction. The faults are composed of multiple secondary faults in en-echelon arrangement; faults in the Permian are mainly along nearly EW and NW direction, and the Permian faults are distributed in the middle east part of the study area and they are more in the north than in the south. (2) The nearly EW and NW trending faults are dextral strike-slip faults, and the NE trending faults are sinistral strike-slip faults. The strike-slip strength of the nearly EW trending faults are the strongest and the maximum horizontal displacement is 550 m, while the strike-slip strength of the NE trending faults is the weakest. The Cambrian faults had stronger activities than the Permian faults. (3) The transtensional strike-slip faults were active in two periods, the early Caledonian period and the late Hercynian period, and were the products of oblique extension of pre-existing weak zones in Xingkai and Emei taphrogenesis, with certain inheritance in the main faults. (4) The strike-slip faults and surrounding fractures enhance the porosity and permeability of the reservoir in Cambrian Longwangmiao Formation and control the distribution of karst reservoirs in the Permian Qixia Formation–Maokou Formation, bringing about the situation of multiple gases bearing series in this area. Key words: Sichuan Basin, Gaoshiti–Moxi area, Cambrian, Permian, strike-slip fault, structural characteristics, gas accumulation

Background Prompt, accurate, and noninvasive prediction of fluid responsiveness is still lacking in intensive care unit. This study is to investigate the value of the Doppler ultrasound evaluation of variation in brachial artery peak velocity (VVpeakbrach) and passive leg raising (PLR)-induced changes in the brachial artery peak velocity (ΔVpeakPLR) in predicting the fluid responsiveness in mechanically ventilated patients with severe sepsis or septic shock. Methods A prospective study was conducted involving 62 patients. Semirecumbent positioning, PLR, and a return to the semirecumbent position were performed with all patients before volume expansion. VVpeakbrach, ΔVpeakPLR, and stroke volume were observed by Doppler ultrasound. A patient with an increase of ≥15% in the stroke volume on volume expansion was defined as a responder. The predictive value was evaluated on the receiver operating characteristic curve analysis. Results A total of 28 patients were classified as responders. The area under the receiver operating characteristic curve of ΔVpeakPLR and VVpeakbrach was 0.898 and 0.891, respectively. A ΔVpeakPLR value of more than 10.6% predicted the fluid responsiveness with a sensitivity of 82.1% and a specificity of 88.2%. A VVpeakbrach value of more than 10.95% predicted the fluid responsiveness with a sensitivity of 78.6% and a specificity of 91.2%. The positive predictive value was 94.4% when both were positive. In contrast, the negative predictive value was 96.6%. Conclusions Doppler ultrasound evaluation of VVpeakbrach and ΔVpeakPLR could be a feasible method for the noninvasive assessment of fluid responsiveness in mechanically ventilated patients with severe sepsis or septic shock. The combination of two indicators can improve the predictive value.

MicroRNA-155 (miR-155) is implicated in the pathological processes of sepsis. However, the function and regulatory mechanism of miR-155 in sepsis-induced inflammation and intestinal barrier dysfunction remain unknown. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). To reduce miR-155 expression, the mice were injected for three consecutive days with an miR-155 inhibitor (80 mg/kg) before CLP. The serum DAO concentration was measured by ELISA, and histological changes in the intestine were identified by H&E staining 24 h after CLP. FITC-dextran assays were used to evaluate intestinal permeability. MiR-155 gene expression was evaluated with RT-PCR, and relative protein expression was assessed by Western blotting. NCM460 cells were transfected with an miR-155 mimic/miR-155 inhibitor or pretreated with an NF-κB inhibitor before LPS treatment, and the cytokines levels, miR-155 gene expression and relative protein expression were measured. Sepsis increased miR-155, DAO and FITC-dextran levels and reduced Occludin and ZO-1 expression. Mice injected with the miR-155 inhibitor recovered from the damages. Transfection of NCM460 cells with the miR-155 mimic elevated the NF-κB (P65) and p-NF-κB (p-P65) localization and expression in the nucleus, which was reversed by the miR-155 inhibitor. Pretreatment with an NF-κB inhibitor suppressed inflammation, improved cell permeability to FITC-dextran and increased Occludin and ZO-1 levels. Transfection with the miR-155 inhibitor decreased TNF-α and IL-6 levels, reduced cell permeability to FITC-dextran and increased ZO-1 and Occludin expression. The effects induced by transfection with the miR-155 mimic, including elevated TNF-α and IL-6 levels, hyperpermeability to FITC-dextran and reduced ZO-1 and Occludin expression, were partly rescued by pretreatment with the NF-κB inhibitor. These findings reveal that the miR-155 inhibitor alleviates inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling during sepsis.

The mechanical behavior of geosynthetic-reinforced and pile-supported (GRPS) embankments is under the influence of the soil arching effect. Several design methods have been proposed for estimating the magnitude of arching for GRPS embankments, but they are usually faced with two limitations: a pre-set constant critical arch height is assumed for the load calculation, and influences of the membrane effect of deflected geosynthetic and the resistance of compressible subsoil are poorly considered in supporting the embankment fill. To improve on these limitations, a new simplified method is presented for quantitatively evaluating the arching action, as well as the geosynthetic tension. During the derivation, the stress state and deformation condition within the arch rib can be coupled by mobilized shearing stress, which is correlated to the differential displacement between the pile (cap) and subsoil. Through comparative studies, it is found that the present method is validated as reasonable by field measurements and is in good agreement with several current design methods.

Background: Due to a scarcity of national epidemiologic data on sepsis, we performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in intensive care units (ICUs) in China. Methods: A national survey was performed in 44 hospitals which were selected by randomization according to the population from each province in mainland China. All septic patients in participating ICUs from December 1, 2015 to January 31, 2016 were included in the analysis. We recorded demographic, physiological and bacteriological data and followed up for 90 days or until death after inclusion. The incidence of and mortality due to sepsis in the ICU was calculated. The relationship between gross domestic product (GDP) and incidence of sepsis was also determined. Findings: Of 2,322 patients with sepsis included in the analysis, 786 (33.85%) patients had hospital-acquired sepsis with the most common infection site being the lung. The incidence of sepsis in the ICU was 20.6[95%CI 15.83-25.37] cases per 100 ICU admissions were diagnosed as sepsis. There was significant variation in the incidence of sepsis in the ICUs of different geographic regions. Ninety-day mortality due to sepsis was 35.49%, which yielded about 81,876 deaths in patients with ICU-treated sepsis every year in the mainland China. There was a significant relationship between the incidence of sepsis in the ICU and GDP per capita (R2=0.304, p=0.001) and the ratio of ICU beds to hospital beds (R2=0.270, p=0.003). Interpretation: Sepsis is a frequently occurring, life-threatening syndrome in the ICU with a high mortality in the mainland of China. Clinical Trial Number: This study was also registered in ClinicalTrials.gov (https://clinicaltrials.gov/show/NCT02448472). Funding Statement: This study was supported by a grant from the Development Center for Medical Science and Technology National Health and Family Planning Commission of the People’s Republic of China (WH2015-01-01), a grant from Jiangsu Provincial Key Medical Discipline (grant number: ZDXKA2016025) and a grant from Jiangsu Provincial Medical Talent (grant number: ZDRCA2016082). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The protocol of this study was approved by the ethics committees of Zhongda Hospital, School of Medicine, Southeast University (No. 2015ZDSYLL044.0), and every enrolled hospital. Patients admitted into the ICU were enrolled in this study following informed consent from the patient or their guardian.

Through analyzing the nature and periods of Tongwan tectonization, by using seismic data, drilling data and outcrop data, the pre-Qiongzhusi Formation eroded paleo-geomorphology was described with remaining thickness and moldic methods, and the hydrocarbon accumulation conditions were analyzed. The Sichuan Basin and its adjacent areas experienced Tongwan tectonization from late Sinian to early Cambrian which include three episodes that all manifested as regional uplift and erosion, forming three disconformities. Affected by that movement, a large scale Deyang-Luzhou eroded valley in N-S direction was formed in Central-Southern Sichuan Basin. In the valley, thick Maidiping Formation and Qiongzhusi Formation are Cambrian important source kitchens; they form good source-reservoir combinations with two sets of weathering karst reservoirs in Deng 2 and Deng 4 Member in Dengying Formation, favorable for the formation of large gas field with huge resource potential. The analysis of forming mechanism and evolution history of the eroded valley shows the thrusting-fold uplifting and erosion in the second episode of Tongwan tectonization in late Sinian period, and the extensional movement in the background of rapid marine transgression in early Cambrian are key to the formation of the eroded valley. Key words: Tongwan tectonization, paleohigh, Dengying Formation, Qiongzhusi Formation, source-reservoir combination, Sichuan Basin

Spectral properties and inclusion complexes of β-cyclodextrin (β-CD) with nonionic amphiphiles and rigid 1-bromonaphthalene (BrN) was investigated in detail. Fluorescence and 1 H NMR measurements give new insights into inclusion of the hydrophobic moiety of amphiphiles into the cavity of β-CD. Their apparent stability constants were well correlated with the structure of the hydrophobic moiety of amphiphiles. The long and flexible hydrophobic moiety may occupy the cavity in the compressed manner. The phosphorescence quenching and the binding strength of BrN in ternary complexes indicate that the inclusion depth and the rigidity of BrN in the cavity of β-CD are predominant factors in determining its phosphorescence. Further inclusion of rigid BrN into the cavity drives the built-in phenyl group of amphiphiles to expose to bulk water phase to a greater extent. Comparative analyses of molecular sizes and models reveal that the flexible hydrocarbon chain of an amphiphile in supramolecular inclusion complexes was located inside the crowded cavity of β-CD due to the filling of rigid BrN into the cavity.

The binding of polyethylene glycol (10) n-octylphenyl ether (OPE) and polyethylene glycol (10) tert-octylphenyl ether (Triton X-100, TX) to beta-cyclodextrin (beta-CD) and heptakis(2,3- beta-dimethyl)- beta-CD (DM- beta-CD) was described in detail by surface tension, steady-state fluorescence of OPE and TX, and phosphorescence of 1-bromonaphthalene (BN) probe. Surface tension and fluorescence measurements show that beta-CD entraps the hydrophobic moieties of OPE and TX to form inclusion complexes with the stoichiometry of 1:1. Unlike the n-octyl group of OPE, however, the tert-octyl group of TX fails to be encapsulated into the cavity of DM- beta-CD because of the steric hindrance of methyl groups at the rim of the cavity. The inclusion of the phenyl group of OPE and TX was demonstrated by dynamic quenching effect of iodide ion on fluorescence of OPE and TX in the presence of beta-CD. Static fluorescence quenching of OPE and TX by BN, phosphorescence of BN, and energy transfer between TX and BN provide additional evidence for the inclusion of their phenyl groups into the CD cavity. Analyses of molecular size suggest that the longer tert-octyl group of OPE is situated in curled manner in the cavity and the tert-octyl group of TX undergo a slight distortion for fit of beta-CD. Further introduction of the third guest component into the CD cavity occupied by OPE and TX will force the flexible octyl groups of OPE and TX to deform to a greater extent.