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Abstract Background Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce. Methods CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J). Different doses (10 mg/kg, 20 mg/kg, and 30 mg/kg) and injection methods (subcutaneous/intraperitoneal/gavage injection) of tamoxifen were used to induce the construction of NCSTN knockout mice (mice model). The expressions of nicastrin, NICD1, hes1 in skin, brain, and liver tissue in mice model and wild-type (WT) mice were measured by qRT-PCR and IHC. Results The construction of mice model was successfully induced by tamoxifen, knockout efficiency was 93%, there was no difference in knockout efficiency among three doses, injection methods, genders (P > 0.05). HS-like lesions appeared on the skin of NCSTN knockout mice after 1 month of treatment with tamoxifen, male mice had a higher number of skin lesions compared to female mice (male vs female = 76.5% vs 41.7%, P = 0.027). Compared with WT mice, the expressions of nicastrin (skin P = 0.0009, brain P = 0.0194, liver P = 0.0066), NICD1 (skin P = 0.0115, brain P = 0.0307, liver P = 0.008), hes1 (skin P = 0.0476, brain P = 0.0143, liver P = 0.0003) in mice model all decreased. Conclusions The NCSTN knockout mouse might be employed as HS animal model; Reducing nicastrin may affect the expression of notch1–hes1 pathway molecules in skin, brain, and liver tissues; low dose (10 mg/kg/d) tamoxifen could be used to induce the deletion of the target gene in mice.

Abstract Background Early evaluation of radiation sensitivity in lung cancer patients can facilitate the transition to personalized treatment strategies. To this end, we assessed the capability of 89Zr-anti-γH2AX-TAT microPET imaging in determining the radiosensitivity of lung cancer xenograft models. We prepared and conducted quality control on 89Zr-anti-γH2AX-TAT. The radiosensitivity of human non-small cell lung cancer cells (H460) and adenocarcinoma cells (A549) was analyzed through clonogenic survival experiments. Additionally, the role of γH2AX as a biomarker for radiosensitivity was validated by quantifying γH2AX foci via fluorescence staining. Subsequently, the H460 and A549 xenograft mouse models were subjected to irradiation, followed by 89Zr-anti-γH2AX-TAT microPET imaging. Concurrently, we performed immunofluorescence staining for γH2AX in tumor tissues to establish a correlation between the uptake of 89Zr-anti-γH2AX-TAT and γH2AX expression. Results The surviving fraction 2 Gy (SF2) values of H460 and A549 indicating that A549 adenocarcinoma has higher radiosensitivity. The cell immunofluorescence experiment showed that the repair of γH2AX foci in H460 cells after irradiation was significantly higher than that in A549 cells, which also confirmed that A549 has higher radiosensitivity. The microPET imaging results showed the uptake of 89Zr-anti-γH2AX-TAT in the tumor of the A549 models after radiotherapy was higher than H460 models. The immunofluorescence staining of tumor tissue confirmed that the expression level of γH2AX was higher and the correlation with microPET imaging uptake was good. Conclusion 89Zr-anti-γH2AX-TAT allows PET imaging of radiosensitivity in lung cancer xenograft models, and is expected to become an early evaluation method for lung cancer radiosensitivity.

AbstractSandy dolomite strata are widely distributed in the diversion tunnel of the Yuxi section of the Water Diversion Project in Central Yunnan (WDPCY). The water-sand inrush is the main failure phenomenon in the construction of sandy dolomite tunnel, which has seriously and commonly threatened the safety of the Chenaju (CNJ) tunnel in the WDPCY. In this paper, we established the discriminant matrix of the water-sand inrush risk assessment by consulting the experts, including the designers and construction personnel of the CNJ tunnel. Then, the risk assessment of water-sand inrush in the CNJ tunnel is carried out based on the proposed Fuzzy-AHP method. The results show that (1) a hierarchical model for risk assessment of water-sand inrush in sandy dolomite tunnel is constructed by criterion and index including thirteen factors. (2) The main criterion layer factors affecting water-sand inrush in the sandy dolomite tunnel are dolomite’s sandy degree and water yield. (3) The risk grade of water-sand inrush in the sections of YX49 + 089∼YX49 + 099 and YX51 + 637∼YX51 + 647 in the CNJ tunnel is V, which indicates very high risk. The assessment results are consistent with the actual engineering situation, which indicate the proposed method can provide the reference for the risk management in a similar project.Key Policy HighlightsThirteen main factors induce water-sand inrush in sandy dolomite tunnel.Characteristics of sandy dolomite mass and groundwater condition play a decisive role in sandy dolomite tunnel for water-sand inrush.A water-sand inrush risk assessment system established based on Fuzzy-AHP method is suitable for sandy dolomite tunnel.

The efficiency of industrial knowledge transfer (IKT) directly affects the level of knowledge connection and collaborative innovation in the industry. However, there is a lack of research, particularly from the perspective of network characteristics, to investigate the efficiency of IKT. Therefore, this study proposes a methodology for measuring the efficiency of weighted industrial knowledge transfer network (IKTN) by employing multiple network indicators. Firstly, based on patent data, a weighted IKTN model with node and edge weights is constructed, and the weighted clustering coefficient and path length of the network are defined. Then, considering the indicators of node weights, edge weights, weighted clustering coefficient, and path length, an efficiency measurement model for the weighted IKTN is established. Finally, we take the environmental protection industry (EPI) in the Yangtze River Delta region of China as the practical case to verify the scientific validity and applicability of the proposed method. The results show that the measurement method proposed can effectively evaluate the node efficiency and overall efficiency of IKTN, and provide a scientific basis for relevant policymaking. This study comprehensively considered multiple factors in the IKTN efficiency measurement and used existing data from the patent database in the weight setting, avoiding the problem of excessive reliance on subjective factors in previous studies that may lead to deviations in the authenticity of the evaluation.

Abstract Background Carotenoid cleavage oxygenases (CCOs) include the carotenoid cleavage dioxygenase (CCD) and 9-cis-epoxycarotenoid (NCED), which can catalize carotenoid to form various apocarotenoids and their derivatives, has been found that play important role in the plant world. But little information of CCO gene family has been reported in litchi (Litchi chinensis Sonn.) till date. Results In this study, a total of 15 LcCCO genes in litchi were identified based on genome wide lever. Phylogeny analysis showed that LcCCO genes could be classified into six subfamilies (CCD1, CCD4, CCD7, CCD8, CCD-like, and NCED), which gene structure, domain and motifs exhibited similar distribution patterns in the same subfamilies. MiRNA target site prediction found that there were 32 miRNA target sites in 13 (86.7%) LcCCO genes. Cis-elements analysis showed that the largest groups of elements were light response related, following was plant hormones, stress and plant development related. Expression pattern analysis revealed that LcCCD4, LcNCED1, and LcNCED2 might be involving with peel coloration, LcCCDlike-b might be an important factor deciding fruit flavor, LcNCED2 and LcNCED3 might be related to flower control, LcNCED1 and LcNCED2 might function in fruitlet abscission, LcCCD4a1, LcCCD4a2 , LcCCD1, LcCCD4, LcNCED1, and LcNCED2 might participate in postharvest storage of litchi. Conclusion Herein, Genome-wide analysis of the LcCCO genes was conducted in litchi to investigate their structure features and potential functions. These valuable and expectable information of LcCCO genes supplying in this study will offer further more possibility to promote quality improvement and breeding of litchi and further function investigation of this gene family in plant.

ABSTRACT Streptococcus suis is a zoonotic pathogen that causes disease in humans after exposure to infected pigs or pig-derived food products. In this study, we examined the serotype distribution, antimicrobial resistance phenotypes and genotypes, integrative and conjugative elements (ICEs), and associated genomic environments of S. suis isolates from humans and pigs in China from 2008 to 2019. We identified isolates of 13 serotypes, predominated by serotype 2 (40/96; 41.7%), serotype 3 (10/96; 10.4%), and serotype 1 (6/96; 6.3%). Whole-genome sequencing analysis revealed that these isolates possessed 36 different sequence types (STs), and ST242 and ST117 were the most prevalent. Phylogenetic analysis revealed possible animal and human clonal transmission, while antimicrobial susceptibility testing indicated high-level resistance to macrolides, tetracyclines, and aminoglycosides. These isolates carried 24 antibiotic resistance genes (ARGs) that conferred resistance to 7 antibiotic classes. The antibiotic resistance genotypes were directly correlated with the observed phenotypes. We also identified ICEs in 10 isolates, which were present in 4 different genetic environments and possessed differing ARG combinations. We also predicted and confirmed by PCR analysis the existence of a translocatable unit (TU) in which the oxazolidinone resistance gene optrA was flanked by IS1216E elements. One-half (5/10) of the ICE-carrying strains could be mobilized by conjugation. A comparison of the parental recipient with an ICE-carrying transconjugant in a mouse in vivo thigh infection model indicated that the ICE strain could not be eliminated with tetracycline treatment. S. suis therefore poses a significant challenge to global public health and requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation. IMPORTANCE S. suis is a serious zoonotic pathogen. In this study, we investigated the epidemiological and molecular characteristics of 96 S. suis isolates from 10 different provinces of China from 2008 to 2019. A subset of these isolates (10) carried ICEs that were able to be horizontally transferred among isolates of different S. suis serotypes. A mouse thigh infection model revealed that ICE-facilitated ARG transfer promoted resistance development. S. suis requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation.

Abstract Background This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH). Methods Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed. Results In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up. Conclusion Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.

Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis. Compared to P. multocida, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis. The mean area under the concentration-time curve/MIC (AUC24h/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida, whereas they were 14.6 and 37.8, respectively, for H. parasuis. Danofloxacin AUC24h/MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis. At the current dose of 2.5 mg/kg, the PK/PD cutoff (COPD) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of > 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.

Abstract Background The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer’s disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated. Methods Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed. Results Compared with controls, treated mice had a significant improvement in learning and memory, an elevation of VPS35 levels, and improved synaptic integrity. Additionally, the same animals had a significant decrease in Aβ levels and deposition, reduced tau phosphorylation and less astrocytes activation. Conclusions Our study demonstrates that the enhancement of retromer function by pharmacological chaperones is a potentially novel and viable therapy against AD.

Secondary glioblastomas (sGBM) are derived from previously lower-grade [World Health Organization (WHO) grades II or III] gliomas. Lower-grade benign-behaving gliomas may retain their former grade following recurrence, or may become malignant higher-grade glioblastomas. Prediction of tumor behavior in lower-grade gliomas is critical for individualized glioma therapy. A total of 89 patients were included between January 2000 and January 2019 in the present study to establish a nomogram via univariate and multivariate logistic regression analyses. Nomogram predictive performance was tested in the validation group. We then analyzed 36 O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated lower-grade gliomas from patients seen at West China Hospital of Sichuan University. Survival statistics were calculated with the Kaplan-Meier method. Two clinical factors (molecular diagnosis and WHO grade), five radiological factors (location, cortical involvement, multicentricity, uniformity, and margin enhancement), one biomarker (1p19q codeletion), and a combination of three biomarkers (IDH+/ATRX-/TP53-) were associated with glioma upgrading. Nomograms positive for these prognostic factors had an AUC of 0.880 in the derivation group and 0.857 in the validation group. The calibration and score-stratified survival curves for the derivation group and validation group were good. An operational nomogram was published at https://warrenwrl.shinyapps.io/DynNomapp/. The overall survival of secondary gliomas in the MGMT-unmethylated cohort were influenced independently by the use of temozolomide during the treatment of formerly low-grade gliomas (p=0.00096). Clinical and radiological factors and biomarker-based behavior-oriented nomograms may offer a feasible identification tool for the detection of sGBM precursors. This method may further assist neurosurgeons with the stratification of lower-grade glioma cases and thus the development of better, more individualized treatment plans.

Fatal asthma is a rare and potentially fatal disease. This disease requires suitable treatment to achieve rehabilitation, especially when accompanied by other complications, such as a silent chest and severe bronchial spasm. A 36-year-old man presented with a 10-year history of asthma that broke out into persistent asthma attacks and cardiac arrest, and was accompanied by a silent chest for 18 hours. He recovered and was discharged without any sequelae after being treated by a ventilator, hormones, epinephrine, analgesics, sedation, and muscle relaxants. Comprehensive treatment with a ventilator, hormones, epinephrine, analgesics, sedation, and muscle relaxants has a good effect on fatal asthma combined with a silent chest.

This article analyzes the current research status and development trend of intelligent technologies for underground metal mines in China, where such technologies are under development for use to develop mineral resources in a safe, efficient, and environmentally friendly manner. We analyze and summarize the research status of underground metal mining technology at home and abroad, including some specific examples of equipment, technology, and applications. We introduce the latest equipment and technologies with independent intellectual property rights for unmanned mining, including intelligent and unmanned control technologies for rock-drilling jumbos, down-the-hole (DTH) drills, underground scrapers, underground mining trucks, and underground charging vehicles. Three basic platforms are used for intelligent and unmanned mining: the positioning and navigation platform, information-acquisition and communication platform, and scheduling and control platform. Unmanned equipment was tested in the Fankou Lead-Zinc Mine in China, and industrial tests on the basic platforms of intelligent and unmanned mining were carried out in the mine. The experiment focused on the intelligent scraper, which can achieve autonomous intelligent driving by relying on a wireless communication system, location and navigation system, and data-acquisition system. These industrial experiments indicate that the technology is feasible. The results show that unmanned mining can promote mining technology in China to an intelligent level and can enhance the core competitive ability of China’s mining industry. Keywords: Underground, Autonomous, Communication, Navigation, Intelligent

A novel flux charging method and a crucible quenching method were employed to study the mechanism of solid fluxes refining method regarding the removal of oxide inclusions (Al2O3) from molten aluminum. Electrochemical polishing method was adopted to prepare surfaces of the samples. Through experiments, the morphology of the residual solidified flux in the solidified samples as well as the wetting action of the molten flux during refining were observed for the first time. Three wetting regimes denoted by absorbing regime, engulfing regime and penetration regime correlating with the removal of oxide films (the most typical and common oxide inclusions in molten aluminum) were proposed in terms of different types and distributions of oxide films and different size ratios of the molten flux to oxide films. Particularly, from a thermodynamic point of view, for the first time, the penetration regime provided concrete evidence that the practical oxide inclusions can be wet by molten flux under ambient fluid of molten aluminum. A spreading model was proposed, according to which ingredients and size parameters of practical solid fluxes can be optimized.

Background: Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB. Methods: In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28. Results: The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28. Conclusions: As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

Background: The management of pain, agitation, and delirium (PAD) in Intensive Care Unit (ICU) is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed that the clinical practice of PAD in ICU was improving; yet relatively little information is available in China. This study aimed to investigate the practice of PAD in ICUs in China. Methods: A multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and management of PAD by the clinicians in ICUs. The practice of PAD was compared among the four regions of China (North, Southeast, Northwest, and Southwest). The data were expressed as percentage and frequency. The Chi-square test, Fisher's exact test, and line-row Chi-square test were used. Results: Of the 1011 valid questionnaire forms, the response rate was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and confusion assessment method for the ICU were the first choices of scales for PAD assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place (66.07% and 76.36%). Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians (87.24%) used analgesics while using sedatives. Of the 738 (73%) clinicians titrating the sedatives on the basis of the proposed target sedation level, 268 (26.61%) clinicians just depended on their clinical experience. Totally, 519 (51.34%) clinicians never used other nondrug strategies for PAD. The working time of clinicians was an important factor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same. Conclusions: The practice of PAD in China follows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China; however, the trend is consistent. Trial Registration: The study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr. org.cn/index.aspx.).

The influence of cooling rate and Fe-containing phases on Sr-modification of Si phases in hypoeutectic Al-Si alloys, a problem with great industrial importance, was investigated. The microstructures of samples were examined using scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX). A new method of electron probe microanalysis (EPMA) map scanning was used to analyze the Sr distribution, which gave quantitative results covering more Si particles. EPMA map scanning, together with SEM with EDX, was also used in analyzing the distribution of Fe phases. Results show that Fe-containing phase was related to the unmodified Si particles in samples with partial modification failure and the plate-like Si phases in samples without modification failure. Such a relationship was further confirmed by the microstructure observation. In conclusion, a partial failure of Sr-modification can be caused by both slow cooling rate and Fe-containing phases.

Ever increasing mine production capacity and mechanized operations enable advanced drilling equipment to be widely adopted in underground mines. In order to achieve satisfactory blasting performance in tunnel advance, there is a critical need to optimize the blasting technique to match the large deep-hole drilling capability. In this study, through theoretical analysis of tunnel blasting, the layout of cutting holes was found to be the key factor controlling the blasting performance. The deep-hole cutting effect was first investigated by analyzing the influence of the free surface of a hollow hole using the fluid-structure interaction modeling method in ANSYS/LS-DYNA. Then the rock dynamic evolution processes of blasting using a double-cavity grooving and a four-cavity grooving were compared and analyzed towards an understanding of the influence of the spacing and layout of cutting holes on the blasting performance. The comparison results show that four empty hole cut layouts yield larger effective free surface than that of the two empty hole cut layouts. This is because larger compensation space for breaking of rock and expansion of gas is more conducive to improving the energy utilization rate of explosives and thus improving the blasting performance and the footage of cyclic blasting. The results indicated that the blasting performance can be improved by reserving reasonable compensation space in the grooving area.

Background. Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. Methods. A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n=30), UC-MSC group (n=30), PE group (n=30), and UC-MSC + PE group (n=20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). Results. The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P

Background: Sepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis. Methods: This was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated. Conclusions: This study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients. Trial Registration: ClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472.

Background: Inconsistencies in the use of the vasoactive agent therapy to treat shock are found in previous studies. A descriptive study was proposed to investigate current use of vasoactive agents for patients with shock in Chinese intensive care settings. Methods: A nationwide survey of physicians was conducted from August 17 to December 30, 2012. Physicians were asked to complete a questionnaire which focused on the selection of vasoactive agents, management in the use of vasopressor/inotropic therapy, monitoring protocols when using these agents, and demographic characteristics. Results: The response rate was 65.1% with physicians returning 586 valid questionnaires. Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock; and 68.3% of respondents preferred dopamine for cardiogenic shock. Dobutamine was selected by 84.1%, 64.5%, and 60.6% of respondents for septic, hypovolemic, and cardiogenic shock, respectively. Vasodilator agents were prescribed by physicians in the management of cardiogenic shock (67.1%) rather than for septic (32.3%) and hypovolemic shock (6.5%). A significant number of physicians working in teaching hospitals were using vasoactive agents in an appropriate manner when compared to physicians in nonteaching hospitals. Conclusions: Vasoactive agent use for treatment of shock is inconsistent according to self-report by Chinese intensive care physicians; however, the variation in use depends upon the form of shock being treated and the type of hospital; thus, corresponding educational programs about vasoactive agent use for shock management should be considered.

Background and Objective: Ventilator-associated pneumonia (VAP) is still an important cause of morbidity and mortality in mechanically ventilated patients. The efficacy of the probiotics for preventing VAP is still controversial. Present study was conducted to comprehensively evaluate the effect of probiotics on VAP prevention in mechanically ventilated patients.Methods: PubMed, Embase, and CENTRAL were searched up to September 2016. Eligible trials designed with randomized controlled trials (RCTs) comparing probiotics with control in mechanically ventilated patients were included. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were estimated with fixed or random effects models. Trial sequential analysis (TSA) was performed using TSA 0.9beta software.Results: Thirteen RCTs (N = 1969) were included. Overall, probiotics were associated with reduced incidence of VAP (RR = 0.73, 95% CI = 0.60–0.89; P = 0.002), which was confirmed by TSA (TSA adjusted 95% CI = 0.55–0.96). However, no significant difference was observed in 90-day mortality (RR = 1.00, 95% CI = 0.72–1.37; P = 0.99), overall mortality (RR = 0.84, 95% CI = 0.70–1.02; P = 0.09), 28-day mortality (RR = 1.06, 95% CI = 0.72–1.57; P = 0.99), intensive care unit (ICU) mortality (RR = 0.97, 95% CI = 0.74–1.27; P = 0.82), hospital mortality (RR = 0.81, 95% CI = 0.65–1.02; P = 0.07), diarrhea (RR = 0.99, 95% CI = 0.83–1.19; P = 0.92), length of ICU stay (MD = −2.40 days, 95% CI = −6.75 to 1.95; P = 0.28), length of hospital stay (MD = −1.34 days, 95% CI = −6.21 to 3.54; P = 0.59), and duration of mechanical ventilation (MD = −3.32 days, 95% CI = −6.74 to 0.09; P = 0.06).Conclusions: In this meta-analysis, we found that probiotics could reduce the incidence of VAP in mechanically ventilated patients. It seems likely that probiotics provide clinical benefits for mechanically ventilated patients.

AIM:To introduce a modified pterygium excision, so as to improve the operation quality. METHODS:To cut the neck of the pterygiumat at limbus, then tear pterygiumat from opposite direction of head on the basis of the original excision. When resistance occurs, point of a knife(15°knife, pointed blade or diamond knife)was employed for cutting on the direction of tangent to cornea. In the process, the operation gave priority to tearing and was supplemented by cutting. A conjunctival flap was taken from the superior temporal and same size as the cut area. Conjunctival transplantation should be firmly stitched on the sclera. RESULTS:The implementation was taken on 660 eyes. There were only 8 eyes relapsed, and the smoothness and transparency of cornea was superior to the conventional method. Recovery time was shortened obviously. CONCLUSION:The modified method of reversal tear-cutting, conjunctival autograft and sclera reinforcement fixation is more effective than the conventional transplantation for treating pterygiumat.

Up-regulation of CD4+CD25+CD127low/- regulatory T cells (Tregs) is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, meanwhile, heme oxygenase-1 (HO-1) plays an important role in the development and maintenance of CD4+CD25+ regulatory T cells. However the mechanism has not yet been adequately understood. Hence, we wondered what effect of Heme Oxygenase-1 made on regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells. Peripheral blood mononuclear cells isolated from asthmatic patients and healthy controls were co-cultured with human bone marrow mesenchymal stem cells which were pretreated with Hemin (the revulsive of Heme Oxygenase-1), Protoporphyrin Ⅸ zinc (the inhibitor of Heme Oxygenase-1) and saline. The expression of Heme Oxygenase-1 in MSCs was enhanced by Hemin and inhibited by Protoporphyrin zinc in vitro. Overexpression of Heme Oxygenase-1 elevated the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells, meanwhile, inhibition of Heme Oxygenase-1 decreased the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells as compared with mesenchymal stem cells alone. Taken together, these data demonstrated that Heme Oxygenase-1 contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma.

Rock slopes with layered fractured structure are widely distributed in the mountainous areas of Southwest China. Under earthquake, these slopes are highly susceptible to disasters such as collapse, landslides, etc., adversely impacting the operation safety of transportation systems. This study aims to investigate the difference in seismic behaviors of two types of fractured rock slopes with typical dipping and anti-dipping layered structures. To do so, two sets of large-scale shaking table tests on the two typical fractured rock slopes were performed. The emphasis was made on the different failure mechanism of these slopes tested when subjected to four different seismic loadings with step-wise increase in amplitudes up to 0.7 g. We observed a three-stage destabilization process in both cases. For the dipping slope, the initial formation of microcracks and then their rapid development was followed by generation of terraced sliding surface through slope, whereas the formation of microcracks was followed by toppling of rock front until final collapse for the anti-dipping slope. Both slopes exhibit elevation amplification effects upon seismic loads as previously observed in other studies of similar slopes. The acceleration amplification effects near the bedrock interface and within slopes are more significant in the dipping case compared to the anti-dipping one. These effects are much enhanced at the top of slopes considered when the peak input acceleration exceeds 0.4 g. Further, Hilbert marginal spectrum analysis indicates that a sliding failure surface above the midslope was formed for the dipping slope, whereas the anti-dipping slope experienced more severe damages at the slope shoulder. The outcomes of this study are of important potential to assist the risk assessment and early warning of seismic hazards of fractured rock slopes. [ABSTRACT FROM AUTHOR]

AIM: To assess the corneal high-order aberration (HOA) and its correlation with corneal morphological parameters in patients with bilateral keratoconus (KCN) and unilateral Vogt's striae. METHODS: A total of 168 eyes of 84 patients with KCN, whose corneas had definite signs of unilateral Vogt's striae, were enrolled. Corneal HOA and morphological parameters were measured using Pentacam HR. RESULTS: The corneal morphological parameters between KCN eyes with and without Vogt's striae were evidently different (P