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Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

To date, the efficacy of glucocorticoid therapy to reduce mortality in patients with acute respiratory distress syndrome (ARDS) has remained controversial among the studies available. The present meta-analysis study aimed to further clarify the impact of glucocorticoid therapy on mortality in patients with ARDS by performing a pooled analysis of the previous data. The PubMed, Chinese Knowledge Infrastructure, Wanfang and Cochrane trials databases were searched for relevant studies published between 1966 and 2016. Randomized controlled trials (RCTs) that included the use of glucocorticoids in patients with ARDS and had reported on mortality were included. Odds ratios (OR) and 95% confidence intervals (CI) for mortality were calculated. A total of 10 RCTs were included in the meta-analysis. Of these, 4 studies used high-dose glucocorticoid therapy, while 6 used low-dose glucocorticoid therapy. In the pooled analysis, glucocorticoids were indicated to significantly reduce ARDS-associated mortality (OR=0.64, 95% CI: 0.48–0.85, P=0.002). Further subgroup analysis indicated the following: i) Long-term low-dose glucocorticoid therapy reduced ARDS-associated mortality compared with that in the control group (OR=0.60, 95% CI: 0.44–0.82, P=0.001), whereas high-dose short-term glucocorticoid therapy did not reduce mortality (OR=0.82, 95% CI: 0.43–1.57, P=0.55). ii) Early initiation of glucocorticoid therapy was associated with reduced mortality compared with that in the control group (OR=0.60, 95% CI: 0.44–0.83, P=0.002); however, late initiation did not reduce mortality (OR=0.36, 95% CI: 0.03–3.76, P=0.39). iii) Therapeutic rather than preventive use of glucocorticoids reduced mortality (OR=0.65, 95% CI: 0.49–0.86, P=0.003). Overall, the present meta-analysis suggests that early initiation of long-term low-dose glucocorticoid therapy reduces mortality of patients with ARDS.

Coronavirus disease 2019 (COVID-19) becomes a global pandemic in 2020. Early identification of severe ill patients is a top priority for clinicians. We aimed to describe clinical features and risk factors of severe-critically ill patients with COVID-19 in Jiangsu Province.This multi-centered retrospective study collected the information of 631 laboratory-confirmed COVID-19 patients hospitalized at 28 authorized hospitals in Jiangsu province from January 23, 2019 to March 13, 2020.A total of 583 adult patients with laboratory-confirmed COVID-19 were enrolled for final analysis, including 84 severe-critically ill patients and 499 mild-moderate patients. Median age of the severe-critically ill patients was 57.0 years old (interquartile range, 49.0-65.8), and 50 (59.5%) were males. Multisystemic laboratory abnormalities were observed on admission for severe-critically ill patients. These patients showed more noticeable radiologic abnormalities and more coexisting health issues as compared to the mild-moderate patients. Most of the severe-critically ill COVID-19 patients became deteriorated in 2 weeks after diagnosis. Age, D-dimer, and lymphocytes were independently associated with the progression of severe-critically illness.Older age, higher D-dimer levels and less lymphocyte counts on admission are potential risk factors for COVID-19 patients to develop into severe and critically illness.

Subunit 1 is the scaffold protein of the carbon catabolite repressor protein 4 (CCR4)‑negative on TATA (NOT) complex (CNOT1). In our previous study, it was reported that tristetraprolin (TTP) could recruit subunit 7 of the CCR4‑NOT complex (CNOT7) to induce the degradation of intercellular adhesion molecule‑1 (ICAM‑1) and interleukin‑8 (IL‑8) mRNA in human pulmonary microvascular endothelial cells (HPMECs). It was additionally demonstrated that TTP, CNOT7 and CNOT1 formed a complex in HPMECs. However, whether CNOT1 is involved in TTP‑mediated ICAM‑1 and IL‑8 mRNA decay remains unclear. The present study demonstrated that CNOT1 knockdown improved ICAM‑1 and IL‑8 mRNA stabilization and protein expression levels. The immunofluorescence results demonstrated that CNOT1, CNOT7 and TTP are co‑localized in the cytoplasm. CNOT1 silencing abolished CNOT7 and TTP coimmunoprecipitation. However, CNOT7 silencing did not influence CNOT1 and TTP coimmunoprecipitation, and TTP silencing additionally did not influence CNOT1 and CNOT7 coimmunoprecipitation. These results together with the authors' previous study, have identified that CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTP‑mediated ICAM‑1 and IL‑8 mRNA decay.

To design a product with the given product requirement and design objective, there can be alternative ways to propose the detailed design specifications of the product. In the design modeling stage, alternative design cases with detailed specifications can be modeled to fulfill the product requirement and design objective. Therefore, in the design evaluation stage, it is required to perform an evaluation of the alternative design cases for deciding the final design. The purpose of this research is to develop a product evaluation model for evaluating the alternative design cases by integrated evaluating the criteria of functional design, Kansei design, and design for supply chain. The criteria in the functional design group include primary function, expansion function, improved function, and new function. The criteria in the Kansei group include geometric shape, dimension, surface finish, and layout. The criteria in the design for supply chain group include material, manufacturing process, assembly, and supply chain operation. From the point of view of value and cost, the criteria in the functional design group and Kansei design group represent the design value of the product. The criteria in the design for supply chain group represent the supply chain and manufacturing cost of the product. It is required to evaluate the design value and the supply chain cost to determine the final design. For the purpose of evaluating the criteria in the three criteria groups, a fuzzy analytic network process (FANP) method is presented to evaluate a weighted index by calculating the total relational values among the three groups. A method using the technique for order preference by similarity to ideal solution (TOPSIS) is used to compare and rank the design alternative cases according to the weighted index using the total relational values of the criteria. The final decision of a design case can be determined by using the ordered ranking. For example, the design case with the top ranking can be selected as the final design case. Based on the criteria in the evaluation, the design objective can be achieved with a combined and weighted effect of the design value and manufacturing cost. An example product is demonstrated and illustrated in the presentation. It shows that the design evaluation model is useful for integrated evaluation of functional design, Kansei design, and design for supply chain to determine the best design case and achieve the design objective., {"references":["Y. J. Tseng, and Y-S. Chen, \"A Closed-loop Design Model for Sustainable Manufacturing by Integrating Forward Design and Reverse Design,\" International Journal of Social, Behavioral, Educational, Economic and Management Engineering, Vol. 9, No. 7, 2015, pp. 2217-2213.","Y.-J. Tseng, and Y-J Wang, \"A Product Development for Green Logistics Model by Integrated Evaluation of Design and Manufacturing and Green Supply Chain\", ICIME 2013 International Conference on Industrial and Mechanical Engineering (World Academy of Science, Engineering and Technology), London, UK, July 08-09, 2013, vol. 7, no. 7, pp. 420-425.","C. A. Weber, J. R. Current, and W. C. Benton, \"Vendor Selection Criteria and Methods,\" European Journal of Operational Research, vol. 50, pp. 2-18, 1991.","R. G. Kasilingam, and C. P. Lee, \"Selection of Vendors: A Mixed-Integer Programming Approach,\" Computers and Industrial Engineering, vol. 31, no. 1-2, pp. 347-350, 1996.","P. K. Humphreys, Y. K., Wong, and F. T. S. Chan, \"Integrating environmental criteria into the supplier selection process,\" Journal of Materials Processing Technology, vol. 138, pp.349-356, 2003.","G. Akyuz, and E., T. Erman, \"Supply chain performance measurement: a literature review,\" International Journal of Production Research, vol. 48, no. 17, pp. 5137-5155, 2010.","T. L. Saaty, \"Decision Making with Dependence and Feedback: The Analytic Network Process,\" Pittsburgh, PA: RWS Publications, 1996.","C. L. Hwang, and K. Yoon,\"Multiple Attribute Decision Making: Methods and Applications, \" New York: Springer-Verlag, 1981."]}

Tristetraprolin (TTP) is an RNA-binding protein which can bind to the AU-rich elements (AREs) at the 3'-untranslated region (3'-UTR) of target mRNA and promote mRNA deadenylation and degradation. We have shown in a previous study that TTP regulates tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8), both of whose mRNAs have AREs in the 3'-UTR, in human pulmonary microvascular endothelial cells (HPMEC) through destabilizing target mRNAs, nevertheless, the mechanism by which TTP promotes mRNA decay remains unclear. Observations have indicated that TTP can interact with CAF1 (CNOT7/hCAF1 in human), a subunit of the CCR4-NOT complex with deadenylase activity. Another study illustrated that TTP can directly bind to CNOT1, the scaffold subunit of the CCR4-NOT complex. The present study showed that TTP bound to the AREs of ICAM-1 and IL-8 mRNAs and was coimmunoprecipitated with intracellular ICAM-1 and IL-8 mRNAs. TTP, CNOT7 and CNOT1 were coimmunoprecipitated in HPMEC. CNOT7 silencing stabilized ICAM-1 and IL-8 mRNAs and increased ICAM-1 and IL-8 production following TNF-α stimulation. These results, together with our previous study, suggest that CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by TTP in HPMEC.

Based on cooperative game theory, this paper, after taking government subsidy into consideration, analyzes, from the two aspects of waste collection cost and disposal cost, the cooperative game relation between manufacturers and resource recovery companies in the process of recycling of industrial zone wastes as well as the important role that government plays in the recycling cooperation mechanism established between the two sides. After calculation of payoff matrix, it is found out that the difference between manufacturers self-disposal cost and entrusted disposal cost, resource recovery companys waste recovery cost and disposal cost, and government subsidy are the key factors that decide whether the two sides will cooperate with each other. Finally, the paper proposes the measures that will facilitate the cooperation of the two sides, which is of certain guiding significance to build an eco-friendly supply chain and boost the development of circular economy.

Based on cooperative game theory, this paper analyzes, from the two aspects of maximizing benefits and risk control, the interactions of symbiotic industrial enterprises during the process of developing circular economy, before proposing the effective measures to reduce cooperation risks, thus providing industrial enterprises and government with some theoretical guidance and basis for actions for recycling of industrial zone wastes.

Citing the facts concerning the waste discharge reality in Liaoning province, this paper analyzes the characteristics of time variation of the “three wastes”, namely, the industrial wastewater, waste gas and solid wastes, and the factors affecting the discharge of the “three wastes” in the province, and makes predictions of the three wastes by setting up various prediction models, including Grey Forecast Model GM (1, 1), GM (1, n) Model, Exponential Smoothing Model, Multivariate Linear Regression Model, and Time Series Model/ARMA model, the results and errors of which are compared, before determining the final predictions and drawing the conclusion.

In recent years, china are paying attention to the development of the circular economy and the ecological industrial parks, industry, as the industry of the largest emissions of industrial waste, the circular economy is more concern by people. The recovery transport process of industrial waste recycling is the important part of the industrial circular economy, reasonable scheduling solution is the effective means to improve the recovery and processing speed of industrial wastes and make the cost of recycling lower. In this paper, through analysis and research the recovery transport links of industrial waste recycling, points out that the vehicle scheduling problem of industrial waste recycling is the scheduling problem combined full load with not-full load, and for this problem, build vehicle scheduling optimization model, use ant colony optimization algorithm to solve it, and that achieved good results.

Glucocorticoids have been widely used in various inflammatory disorders, and the transcriptional repression of inflammatory mediators has been considered to be the main mechanism of action. However, a previous study showed that dexamethasone inhibited interleukin 8 (IL-8) expression by promoting IL-8 mRNA decay, which implies a posttranscriptional regulation. Nevertheless, by which mechanism dexamethasone destabilized IL-8 mRNA was unclear. Another study indicated that an RNA-binding protein, tristetraprolin (TTP), could be induced by dexamethasone. TTP can bind to AU-rich elements (ARE) in the 3'-untranslated region of target mRNAs and promotes mRNA degradation. So, we speculated that dexamethasone destabilized IL-8 mRNA by upregulating TTP expression. Here, we report that dexamethasone reduced IL-8 expression through destabilizing IL-8 mRNA in human pulmonary microvascular endothelial cells (HPMECs). Dexamethasone stimulation increased TTP mRNA and protein levels. TTP silencing led to mRNA stabilization and protein upregulation of IL-8. These results provide the evidence that the glucocorticoid, in HPMECs, inhibits IL-8 expression through TTP at the posttranscriptional level.

Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, and has become a major public health concern. We report the pneumococcal serotype and sequence type (ST) distribution, and antimicrobial resistance of 39 S. pneumoniae strains from seven hospitals in China.Blood/cerebrospinal fluid (CSF) and sputum isolates from patients were analyzed to determine S. pneumoniae serotypes by polymerase chain reaction (PCR) and the Neufeld Quellung reaction, the multilocus sequence types (MLST) by PCR and sequencing, and susceptibility to antimicrobial agents by the VITEK Gram Positive Susceptibility Card.A total of 39 isolates were collected including 21 blood/CSF and 18 sputum isolates. Conventional serotyping by the Quellung reaction required 749 reactions. In contrast, PCR based typing needed only 106 PCR reactions. The most frequent serotypes from the blood/CSF isolates were 14 (38.1%), 19A (14.3%), 23F (9.5%), and 18C (9.5%). In the sputum isolates the most frequent serotypes were 19F (33.3%), 23F (16.7%), 19A (11.1%), and 3 (11.1%). The incidence of penicillin resistance in the blood/CSF and sputum isolates was 66.7% and 55.6%, respectively. Statistical analysis showed that patients = 5 years old had a higher resistance to penicillin when they compared with the patients = 65 years old (P = 0.011). Serotypes 14, 19A and 19F were significantly associated with penicillin resistance (P0.001). ST320, ST271, and ST876 isolates showed high resistant rates to several antibiotics including penicillin (P = 0.006). All of the isolates of serotype 19A were resistant to both penicillin and erythromycin, and they were all multi-drug resistant (MDR) isolates.The specificity and sensitivity of multiplex-PCR are good, and this method represents a substantial savings of time and money, and can be widely used in the laboratory and clinical practice. Data from this research showed an extremely high prevalence of penicillin resistance and an increasing prevalence of multi-drug resistant (MDR) rate in S. pneumoniae. A distinctive emergence of serotype 19A was observed which was also associated with the increasing prevalence of antimicrobial resistance. Therefore, nationwide surveillance of pneumococcal resistance and serotypes is strongly warranted.

The aim of this study was to review our experience with living related liver transplantation (LRLT) for Wilson's disease. From January 2001 to July 2003 LRLT were performed in 18 patients with Wilson's disease, seven of whom had neurologic complications. The mean age of the patients was 13.5 +/- 2.3 years (range 6 to 20). Before transplantation all recipients displayed low serum ceruloplasmin levels (mean value = 118.4 +/- 32.6 mg/L). The serum ceruloplasmin levels increased to an average of 236.8 +/- 38.5 mg/L after LRLT at the latest evaluation, which ranged between 2 and 32 months after transplantation. A marked reduction in urinary copper excretion was observed in all recipients after transplantation. All recipients are alive and remain well. None have developed signs of recurrent Wilson's disease after a mean follow-up of 18.2 +/- 9.4 months (range 2 to 32 months). The donors were 17 mothers and one father of mean age 34.0 +/- 3.0 years (range 30 to 45 years). The serum ceruloplasmin levels were within normal limits in all donors (mean 226 +/- 27.8 mg/L). Two donors had biliary leakage and percutaneous drainage Grafts included four right lobes without the hepatic middle vein and 14 left lobe grafts with the middle vein. LRLT is a curative procedure for Wilson's disease presenting with fulminant hepatic failure and the others with end-stage hepatic insufficiency. After liver transplantation, the serum ceruloplasmin level increases to the normal range, urinary copper excretion decreases, and neurological manifestations improve to various extents.

Jia-Xin Shi,1 Jia-Shu Li,1 Rong Hu,1 Xiao-Min Li,2 Hong Wang3 1Department of Respiratory Medicine, Lianyungang First People’s Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang, 2Department of Critical Care Medicine, Lianyungang First People’s Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang, 3Department of Respiratory Medicine, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China Abstract: The carbon catabolite repressor protein 4 (CCR4)–negative on TATA (NOT) complex includes multiple subunits and is conserved in the eukaryotic cells. The CCR4–NOT complex can regulate gene expression at different levels. Two subunits of the CCR4–NOT complex, CCR4 and CCR4-associated factor 1 (CAF1), possess deadenylase activity. In yeast, the deadenylase activity is mainly provided by the CCR4 subunit; however, the deadenylase activity is provided by both CCR4 and CAF1 in other eukaryotes. A previous study reported that CAF1 but not CCR4 is required for the decay of a reporter mRNA with AU-rich elements. Our previous study showed that CAF1 is involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression. Both ICAM-1 and IL-8 play crucial roles in acute lung injury. In the present study, we examined the effects of CAF1 deficiency on IL-8 and ICAM-1 expression and acute lung injury in mice. Here we showed that there were no differences between the wild-type and CAF1-knockout mice on phenotypes. The lung histology and protein and mRNA levels of IL-8 and ICAM-1 in unstimulated wild-type mice were comparable to those in unstimulated CAF1-knockout mice. However, lipopolysaccharide stimulation led to more severe lung histological injury and greatly higher IL-8 and ICAM-1 expression in CAF1-knockout mice compared to the wild-type mice. These results, together with our previous study, suggest that CAF1 is involved in the regulation of lipopolysaccharide-stimulated IL-8 and ICAM-1 expression in vivo and affects the progression of acute lung injury. Keywords: CAF1, knockout, mice, acute lung injury, IL-8, ICAM-1

To investigate the current status of atypical pathogen associated infections in community-acquired pneumonia (CAP) in adults, and their clinical attributes.Clinical data, sputum specimens from acute phase, and paired sera from acute- and convalescent-phases of CAP in 153 adult patients were collected from May 2005 to May 2008 in multiple medical centers. Chlamydia pneumoniae (Cpn) IgG antibody, and Legionella pneumophila (LP) mixed IgG, IgA and IgM antibodies were determined by indirect immuno-fluorescent assay. Mycoplasma pneumoniae (Mpn) mixed IgG, IgA and IgM antibodies were determined by passive agglutination assay. All the sputum specimens were routinely cultured for bacterial isolation.Fifty-two (34%) out of the 153 cases were diagnosed as atypical CAP per the paired serum-antibody assay. Forty-seven of the 52 atypical CAP cases were infected by one atypical pathogen, 38 with Cpn, 4 with Mpn, and 5 with LP, while 5 out of the 52 atypical CAP cases were infected by 2 pathogens, Cpn and Mpnin 2, Cpn and LP in 3 cases. Eleven cases (21.2%) out of the 52 patients with atypical pneumonia were complicated with bacterial infection. Except peripheral white blood count was significant increased in the group of typical (bacterial only) pneumonia (WBC10 × 10⁹)/L, P = 0.03), all the other clinical parameters did not show statistically significant difference between the typical and the atypical pneumonia groups.Our data suggest that Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are common pathogens of adult CAP. Chlamydia pneumoniae might be the most frequent atypical pathogen associated with atypical CAP.

Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomial acquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple β-lactamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs).Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods.Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanii strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-Ia was found in 23 strains, and the aac-6'-Ib gene in 19 strains. aac-3-Ia and aac-6'-Ib genes hibernated in three A. baumanii strains that showed no drug-resistant phenotype.A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.