Status of microbiological reports at partial provincial level annual academic conference of healthcare-associated infection from 2015 to 2017 / 中国感染控制杂志

Objective To understand the present status of special reports relating to microbiology at China provincial-level annual academic conference of healthcare-associated infection (HAI), and provide basis for the training and capacity-building of HAI management staff.Methods The conference arrangements for annual academic conference of provincial HAI quality control centers and HAI management societies from January 2015 to May 2017 were collected, and the special reports on microbiology were summarized and analyzed.Results A total of 35 annual academic conferences held by 17 provinces/municipalities directly under the central government/autonomous regions were included in the study, most conferences (42.31％) were concentrated on the fourth quarter. 15 annual academic conferences were related to microbiology report, accounting for 5.91％ of the total reports, reporting time accounted for 4.81％ of total time. There were various forms of microbiological thematic reports, subject reports, literature exchange, and interactive exchange accounted for 68.96％, 24.14％, and 6.90％ respectively. The proportion of topics related to microbiology reports increased to a certain extent, but the proportion of reporting time decreased.Conclusion At present, the proportion and reporting time of microbiology reports in China provincial-level annual academic conference of HAI is relatively low, it is necessary to increase the number of microbiology reports in the future annual conference of HAI.

Molecular characteristics and tracing of hemagglutinin of the first highly pathogenic avian influenza A (H7N9) virus mutant strain infection case in Guizhou Province / 中华传染病杂志

Objective@#To investigate the molecular characteristics and tracing of the hemagglutinin (HA) gene, and to analyze the risk of human infection with influenza virus A (H7N9) in Guizhou Province, so that to provide evidence for the prevention and control of highly pathogenic avian influenza A (H7N9).@*Methods@#Nucleic acids of 5 strains of H7N9 including 1 sample of the patient′s nasopharyngeal swab and 4 samples of the live poultry market (LPM) environment were extracted and HA genes were amplified and sequenced. Then the homology, genetic evolution and the pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of the avian influenza A (H7N9) viruses were analyzed by a series of bioinformatics softwares.@*Results@#Homology analysis revealed that the homologies of nucleotide and amino-acid of the HA gene of H7N9 strains from the patient and LPM in Weining County, Guizhou Province were 99.8% and 99.6%, respectively, while those of 4 strains from LPM were both 100%. The homologies of nucleotide and amino-acid of the HA gene of H7N9 strains were the highest with the strain of A/Guangxi/5/2017 isolated from a Guangxi infected patient (99.7%-99.9% and 99.4%-99.8%, respectively), while those with the strain isolated from LPMs environment at the end of 2016 (A/Environment/Guangdong/C16283222/2016) were 99.0%-99.2% and 98.9%-99.2%, respectively. However, the homologies of nucleotide and amino-acid of the HA gene of H7N9 strains with A/Shanghai/2/2013 recommended by world health organization and the candidate vaccine strain A/Anhui/1/2013 were 96.8%-97.0% and 95.8%-96.2%, respectively. Phylogenetic analysis showed that the 5 strains had the nearest genetic distance to the strain A/Guangxi/5/2017. All the 5 strains cleavage site sequences of HA protein showed mutation of PEVPKRKRTAR↓GLF, and they were highly pathogenic avian influenza viruses mutant strains, which all had mutation of G186V at the receptor binding sites of HA gene, while no Q226L mutation was found. All 5 strains had new mutation of A363S, and new mutations of R56K and I297V were only found in the strain isolated from the patient. Among the five potential glycosylation motifs in the HA, only 421NWT and 493NNT had variation of the position post shift.@*Conclusions@#All the 5 H7N9 strains isolated in Weining County, Guizhou Province are highly pathogenic avian influenza mutative viruses. The current candidate vaccine may not provide a very good protection. The mutations of cleavage site of HA protein, G186V as well as other new mutation sites of HA may enhance the susceptibility and pathogenicity to human beings.

Expression of extracellular matrix metalloproteinase inducer in the unstable plaque of patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.</p><p><b>METHODS</b>The EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.</p><p><b>RESULTS</b>Abundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).</p><p><b>CONCLUSION</b>EMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.</p>

Improvement in cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a beagle heart failure model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Heart failure (HF) is a major cause of morbidity and mortality worldwide, but current treatment modalities cannot reverse the underlying pathological state of the heart. Gene-based therapies are emerging as promising therapeutic modalities in HF patients. Our previous studies have shown that recombinant adeno-associated viral (rAAV) gene transfer of Sarco-endoplasmic reticulum calcium ATPase (SERCA2a) can be effective in treating rats with chronic heart failure (CHF). The aim of this study was to examine the effects of SERCA2a gene transfer in a large HF animal model.</p><p><b>METHODS</b>HF was induced in beagles by rapid right ventricular pacing (230 beats/min) for 30 days. A reduced rate ventricular pacing (180 beats/min) was continued for another 30 days. The beagles were assigned to four groups: (a) control group (n = 4); (b) HF group (n = 4); (c) enhanced green fluorescent protein group (n = 4); and (d) SERCA2a group (n = 4). rAAV1-EGFP (1 x 10(12) microg) and rAAV1-SERCA2a (1 x 10(12) microg) were delivered intramyocardially. SERCA2a expression was assessed by Western blotting and immunohistochemistry.</p><p><b>RESULTS</b>Following 30 days of SERCA2a gene transfer in HF beagles its protein expression was significantly higher than in the HF group than in the control group (P < 0.05). Heart function improved along with the increase in SERCA2a expression. Left ventricular systolic function significantly improved, including the ejection fraction, left ventricular systolic pressure, maximal rate of rise of left ventricular pressure (+dp/dt(max)), and the maximal rate of decline of left ventricular pressure (-dp/dt(max)) (P < 0.05). Left ventricular end-diastole pressure significantly decreased (P < 0.05). The expression of SERCA2a in the myocardial tissue was higher in the SERCA2a group than in the HF group (P < 0.05).</p><p><b>CONCLUSIONS</b>Intramyocardial injection of rAAV1-SERCA2a can improve the cardiac function in beagles induced with HF. We expect further studies on SERCA2a's long-term safety, efficacy, dosage and the optimization before using it in humans with HF.</p>

Overexpression of sarcoplasmic reticulum calcium ATPase induced hemodynamic and proteomic changes in a dog model of heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>Overexpression of SERCA2a could improve cardiac function in human and experimental heart failure (HF) models. We observed the proteomics changes post SERCA2a overexpression in a pacing induced HF model in dogs.</p><p><b>METHODS</b>Beagles were divided into four groups: control group, HF group (230 beats/min for 4 weeks), HF + EGFP group (myocardial injection of 1 x 10(12) v.g recombinant adeno-associated virus carrying enhanced green fluorescent protein gene, rAAV2/1-EGFP) and HF + SERCA2a group (myocardial injection of 1 x 10(12) v.g recombinant adeno-associated virus carrying SERCA2a gene, rAAV2/1-SERCA2a). Thirty days after gene transduction, left ventricular systolic and diastolic functions were measured by echocardiography and invasive hemodynamics in all animals. By use of 2-dimensional gel electrophoresis (2-DE), -500 distinct protein spots were detected in myocardium of all animals. Protein spots observed to be altered between failing and SERCA2a overexpressed hearts were subjected to tryptic peptide mass fingerprinting for identification by MALDI-TOF mass spectrometry in combination with LC/MS/MS analysis.</p><p><b>RESULTS</b>At 30 day after gene transfer, HF signs were significantly reduced, cardiac function [LVSP: (214.72 +/- 31.74) mm Hg (1 mm Hg = 0.133 kPa) vs. (139.32 +/- 36.79) mm Hg, +dp/dt(max): (6779.43 +/- 217.58) mm Hg/s vs. (2746.85 +/- 931.23) mm Hg/s and -dp/dt(max): (-4341.42 +/- 322.02) mm Hg/s vs. (-2531.14 +/- 616.15) mm Hg/s, LVEDP: (21.86 +/- 6.95) mm Hg vs. (59.78 +/- 6.92) mm Hg] significantly improved in HF + SERCA2a dogs than those in HF + EGFP group(all P < 0.05) and parameters were comparable between HF + SERCA2a and control groups. We identified alterations in the expression level of more than 10 proteins in myocardium. These protein changes were observed mainly in two subcellular compartments: the cardiac contractile apparatus and metabolism/energetics.</p><p><b>CONCLUSION</b>These results showed that overexpression of SERCA2a could improve cardiac function accompanied with numerous alterations in protein expressions involved in calcium handling, myofibrils, and energy production in this dog model of chronic heart failure.</p>