Abstract: Objective　To investigate the influences of notoginsenoside R1 (NGR1) on cell injury and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway of alveolar epithelial cells infected by Klebsiella pneumoniae (Kp). Methods　A549 cells were grouped into five groups: control group (C group), infection group (Infect group), infection + low NGR1 group (Infect + L-NGR1 group), infection + high NGR1 group (Infect + H-NGR1 group), and infection+high NGR1+JAK2/STAT3 pathway inhibitor group (Infect+H-NGR1+SD-1029 group). Cell proliferation was measured using CCK8; ELISA kits were applied to detect the contents of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in the culture medium; flow cytometry was applied to detect apoptosis; RT-qPCR was applied to detect the expressions of JAK2/STAT3; Western blot was applied to detect JAK2/STAT3 pathway, autophagy protein microtubule-associated protein 1 light chain 3 (LC3), autophagy-relatedgene5 (Atg5), autophagy-related gene (Atg) 6 (Beclin-1), apoptosis protein B-cell lymphoma 2 (Bcl-2), Bcl-2-accociated protein (Bax), cysteinyl aspartate specific proteinase (cleaved-caspase-3) proteins expression. Results　Compared with the C group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect group were obviously decreased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Compared with Infect group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect+L-NGR1 group and Infect+H-NGR1 group were obviously increased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-Caspase-3 were obviously decreased (P<0.05). Compared with Infect+H-NGR1 group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the protein phosphorylation levels of JAK2, STAT3 in the Infect+H-NGR1+SD-1029 group were obviously decreased (P<0.05), and the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Conclusions NGR1 can activate the JAK2/STAT3 signaling pathway, promote autophagy of alveolar epithelial cells, and inhibit Kp-induced inflammatory injury and apoptosis of alveolar epithelial cells.

Cerebrovascular disease is one of the leading causes of death and disability across the world. Vascular homeostasis and recovery is critical to the body. Klotho is an important endogenous pleiotropic protein involved in a variety of pathophysiological processes,such as aging and calcium and phosphorus metabolism,which is closely associated with vascular disease. Recent clinical studies have demonstrated close links between low Klotho levels and various risk factors for cerebrovascular disease,suggesting that Klotho has the potential of predicting the risk of ischemic and hemorrhagic cerebrovascular diseases and poor prognosis. Basic studies have also shown that Klotho plays a crucial role in the maintenance of vascular homeostasis. Klotho can promote the production of nitric oxide,inhibit the expression of inflammatory factors,and mediate antioxidant and anti-aging effects,which can delay atherosclerosis and vascular calcification. Therefore,Klotho may serve as a new target for the prevention and treatment of cerebrovascular disease. This review provides an overview of the relationship between Klotho and cerebrovascular disease and its potential biological mechanisms.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END⁺/Gal⁺-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

OBJECTIVE: To analyze the characteristics of skeletal muscle cells gene markers in septic patients by using bioinformatics. METHODS: The differential gene expression of marker microarrays (GSE13205) in skeletal muscle tissue of patients with sepsis was obtained from gene expression omnibus (GEO) database of National Center for Biotechnology Information (NCBI). Gene differential expression analysis was carried out using online GEO2R provided by NCBI. Data processing, analysis and mapping were carried out using online bioinformatics array research tool (BART) and Cytoscpe software, the software of the national resource for network biology. Functional annotation and pathway analysis of differential expression genes were performed using Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) provided by the database for annotation, visualization and integrated discovery (DAVID), and protein interaction analysis was further performed in search tool for the retrieve of interacting genes/proteins (STRING-DB). RESULTS: The TOP250 genes were extracted from the GSE13205 dataset. A total of 242 differentially expressed genes were included in the analysis. Among them, 78 up-regulated genes and 164 down-regulated genes were identified. After extensive data analysis, these differentially expressed genes were enriched into different biological processes or subsets of molecular functions, mainly enriched in the positive and negative regulation of growth, mineral absorption and other pathways. The 14 most closely related genes among differentially expressed genes were identified from the protein interaction network. CONCLUSIONS The differential expression genes in patients with sepsis were mainly concentrated on cell growth and apoptosis and mediating tumor-related immune function regulation.
Computational Biology ; Gene Expression Profiling ; Gene Ontology ; Gene Regulatory Networks ; Genetic Markers ; Humans ; Muscle, Skeletal/metabolism* ; Sepsis/genetics*

Objective To evaluate the expression and clinical significance of plasma circulating microRNA-23b in patients with myasthenia gravis (MG).Methods Plasma samples from 32 MG patients and 32 healthy people were collected in the Second Affiliated Hospital of Harbin Medical University from October 2015 to August 2016. Expression of microRNA-23b was detected by quantitative reverse transcription polymerase chain reaction .The relationship among microRNA-23b expression level, clinical features and quantitative myasthenia gravis score ( QMG ) was analyzed. Results The expression of circulating microRNA-23b in plasma was significantly higher in MG patients (4.587 (3.654, 5.423)) compared with control group (2.889 (1.968, 4.027), Z=-4.169, P<0.01), meanwhile it was positively related to QMG (r=0.661,P<0.01).But the expression of circulating microRNA-23b had no statistically significant difference in MG subgroups .Conclusion Plasma circulating microRNA-23b is highly expressed in MG and has positive correlation with MG severity .

Objective To investigate the expression level of thymus microRNA-27a-3p in patients with myasthenia gravis (MG) and to explore the pathogenesis of MG.Methods Thymus tissue samples from 36 cases were collected from December 2014 to February 2015 in the Second Affiliated Hospital of Harbin Medical University.Nineteen thymus tissue samples of MG group were collected from department of chest surgery,17 thymus tissue samples of control group were collected from department of chest surgery or congenital heart disease patients from department of cardiac surgery.The expression of microRNA-27a-3p in the thymus from 36 patients was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR),using U6 as housekeeping control.The Wilcoxon Rank-Sum test was used to analyze the relative expression of microRNA-27a-3p of the two groups.Spearman rank correlation was used to determine the correlation coefficient between microRNA-27a-3p and Quantitative Myasthenia Gravis Score (QMGS).Results (1) The expression level of microRNA-27a-3p in thymus was significantly higher in MG group (0.195(0.049,0.714)) compared with control group (0.045(0.004,0.088),Z =-2.646,P =0.008).(2) Nineteen MG patients were included in the study,out of which 7 were ocular myasthenia gravis (OMG) patients and 12 were generalized myasthenia gravis (GMG) patients.The expression of microRNA-27a-3p in GMG patients (0.493 (0.157,1.123)) was significantly higher than that in OMG patients (0.035 (0.008,0.103),Z =-2.620,P =0.009).(3) There was a positive correlation between the expression of microRNA-27a-3p and QMGS (r =0.576,P =0.010).Conclusions The expression of microRNA-27a-3p in thymus is significantly up-regulated in the patients with MG.MicroRNA-27a-3p may be associated with MG severity and significantly elevated in GMG patients compared with OMG patients.

Objective To investigate the association between myasthenia gravis (MG) and single nucleotide polymorphisms (SNPs) of PTPN22 + 1858C/T,CTLA-4 (+ 49A/G;-1772C/T;-1661A/G),KRAS(rs9226),BCL2(rs4987855) and IGF-1R(rs34804698) genes.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was adopted to detect the gene types of SNPs in 76 MG patients who were enrolled in the Second Affiliated Hospital of Harbin Medical University from July 2011 to June 2015 and 59 healthy blood donors.Results In MG patients,the frequences of CTLA-4 +49A/G(rs231775) (57.9％) and-1772C/T (rs733618) (43.4％) were higher than that in the healthy controls (22.1％) (x2 =35.252,P =0.000; x2 =4.098,P =0.043).The frequence of CTLA-4 +49A/G in MG patients combined with thymoma (25.6％) was higher than other subgroups (thymic hyperplasia group:13.8％; normal thymus group:18.4％)(x2 =7.564,P=0.006; x2 =7.155,P=0.007).Meanwhile,the frequence of the C-1772 allele was higher in thymoma group (19.7％) compared with other two groups (thymic hyperplasia group:9.86％ ; normal thymus group:13.8％) (x2 =5.331,P =0.021 ;x2 =4.411,P =0.036).However,the other SNPs were not associated with the risk of MG.Conclusion There are associations of MG with CTLA-4 + 49A/G and-1772C/T SNPs,but not with PTPN,KRAS,BC12 and IGF-1R SNPs.

Objective To explore the direct economic loss caused by healthcare-associated infection(HAI)in general hospitals in China.Methods 68 hospitals were selected,a retrospective 1:1 matched survey was conducted to compare the direct medical cost in patients with and without HAI between January 1,2015 and December 31,2015. Results A total of 2 123 pairs of patients with and without HAI were included in the survey.The average cost of hospitalization in HAI and non-HAI groups were ￥25 845.30 and ￥12 006.14 respectively,￥13 839.16 on average was increased due to HAI.The average economic loss in provincial and ministerial levels of hospitals were￥21 409.83.The average economic loss in different regional hospitals were ￥9 725.42-￥18 909.59,and north China ranked the first.Economic loss caused by bloodstream infection and lower respiratory tract infection were more than other sites,which were ￥23 190.09 and ￥18 194.50 respectively.Conclusion HAI resulted in considerable direct economic loss.Prevention and control of HAI,especially bloodstream infection and lower respiratory tract infection should be paid more attention.

Objective To improve hand hygiene (HH)compliance of health care workers (HCWs)in neonatal in-tensive care units(NICUs)in China through a series of intervention measures.Methods A multicenter study was conducted,17 tertiary first class hospitals in 9 provinces and cities were selected,HH compliance of HCWs in these hospitals were investigated every month according to HH investigation method of World Health Organization.From October 1 ,2013 to March 31 ,2014 was pre-intervention stage;from April 1 ,2014 to September 30,2014 was post-intervention stage,timely feedback and intensified training were conducted at post-intervention stage.Results HH compliance rates of HCWs before and after intervention were 80.29% and 80.85% respectively,there was no sig-nificant difference (P >0.05).HH compliance rates of HCWs in different sizes of ICUs were significantly different before and after intervention (all P <0.05),in NICUs with<20 beds and 20-30 beds after the intervention were both significantly higher than before intervention (both P <0.05 ),while >30 beds were significantly lower than before intervention(P <0.001 );HH compliance rate of cleaners increased from 58.82% before intervention to 68.09% after intervention (P <0.05 );Of different hand hygiene indications,except before clean/aseptic task, compliance to the other HH indications were significantly different between before and after intervention(all P <0.05).Conclusion HH compliance is high among HCWs in NICUs in China,intervention measures,such as inten-sified training and timely feedback have certain influence in compliance to HH among HCWs at different sizes of ICUs,of different occupations,and at different HH indications.

Objective To investigate the epidemiological characteristics of device-associated infection (DAI)in neonatal intensive care units(NICUs)of tertiary first-class hospitals in China,and provide scientific evidence for the prevention and control of neonatal DAI.Methods Neonates in NICUs at 17 hospitals of 9 provinces from October 2013 to September 2014 were selected for multicenter study,DAI was surveyed prospectively according to the uni-form diagnostic criteria and methods.Results A total of 12 998 neonates were monitored,the total patient-days were 126 125 d,13 cases of central line-associated bloodstream infection (CLABSI)and 70 cases of ventilator-asso-ciated pneumonia (VAP)occurred,central line utilization rate was 15.56%,incidence of CLABSI was 0.66/1 000 device-days;ventilator utilization rate was 7.67%,incidence of VAP was 7.23/1 000 device-days.Utilization rates of central line and respirator in neonates with body weight ≤ 1 000 g was the highest,which were 61 .06% and 29.91 % respectively;In NICUs with 20-30 beds,utilization rate of central line was the highest(16.67%),and res-pirator was the lowest(4.11 %);of hospitals in different regions,central line and respirator utilization rate in south-west China was the highest.Of different sizes of ICUs,VAP per 1 000 device-days was the lowest in NICUs with 20-30 beds(2.36 ‰).Difference in incidence of CLABSI and VAP per 1 000 device-days in neonates at NICUs of different regions were significantly different;incidence of CLABSI and VAP per 1 000 device-days was highest in southern China(2.68 ‰ and 31 .06‰ respectively),followed by southwest region.Of different quarters,incidence of CLABSI,and VAP per 1 000 device-days were not significantly different(all P >0.05).Conclusion Device utili-zation rate and incidence of DAI in China are both high,and are different in neonates of different birth weight,at different sizes of NICUs,as well as different regions,monitoring should be intensified,prevention and control measures should be implemented according to infection characteristics.