The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Surveillance of antimicrobial resistance in the bacterial strains isolated from hospitals in Dongguan, Guangdong Province: 2015 report / 中国感染与化疗杂志

Objective To survey the resistance profile of clinical isolates to antibiotics across the hospitals in Dongguan,Guangdong Province during 2015.Methods Kirby-Bauer method or automated system was used to test the susceptibility of clinical isolates to selected antimicrobial agents.Results were analyzed according to CLSI 2015 breakpoints.The susceptibility data were analyzed using WHONET 5.6 software.Results A total of 29 665 strains of microorganisms were isolated,of which gram positive cocci accounted for 32.1％ (9 509/29 665) and gram negative bacilli accounted for 67.9％ (20 156/29 665),respectively.The prevalence of methicillinresistant Staphylococcus was 23.3％ (705/3 024) in S.aureus and 43.6％ (1 054/2 419) in coagulase-negative Staphylococcus.No vancomycin-resistant staphylococcal strain was found.ESBLs-producing strains accounted for 36.4％ (2 554/7 020) in E.coli and 24.5％(792/3 227) in Klebsiella isolates.The prevalence of carbapenem-resistant Enterobacteriaceae was 0.2％ (30/13 077).The prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) was 16.0％ (500/3 116) and 53.9％ (827/1 533),respectively.The prevalence of penicillin-resistant S.pneumoniae (PRSP) strains was 10.1％ (142/1 404).Beta-lactamase was produced in 30.6％ (276/902) of the H.influenzae strains.The prevalence of vancomycin-resistant Enterococcus (VRE) strains was 0.7％ (10/1 441).Conclusions Periodic surveillance of antimicrobial resistance is valuable for rational antimicrobial therapy,formulation of treatment guidelines and infection control and prevention measures,as well as preventing the spread of drug-resistant strains.

Serotypes and antimicrobial resistance profile of the Group B Streptococcus isolates in perinatal pregnant women during the period from 2013 to 2014 / 中国感染与化疗杂志

Objective To analyze the serotypes and antimicrobial susceptibility profile of Group B Streptococcus (GBS) in perinatal pregnant women.Methods The vaginal and rectal specimens were collected from pregnant women at 35 to 37 weeks of pregnancy for culture and identification.The serotypes were analyzed using agglutination assay.Antimicrobial susceptibility testing was conducted by using Kirby-Bauer method,and interpreted according to 2009 CLSI breakpoints.The data were analyzed via WHONET 5.6 software.Results The prevalence of GBS was 10.4％ (264/2 533) in the 2 533 perinatal pregnant women.Serotype Ⅲ,Ⅰa and Ⅰb was identified in 54.9％ (84/153),17.6％ (27/153) and 13.1％ (20/153) of the GBS,respectively.All the GBS isolates were susceptible to penicillin,cefiriaxone and vancomycin.But 32.9％,68.1％ and 62.1％ of the isolates were resistant to levofloxacin,erythromycin and clindamycin,respectively.The antibiotic resistance rate of serotype Ⅲ isolates to the above three antibiotics was significantly higher than the other serotypes.Conclusions GBS may colonize both vagina and rectum of pregnant women.Vaginal and rectal secretions should be sampled simultaneously for better screening GBS.GBS serotype Ⅲ was the predominant serotype.Penicillin can be used as the first-choice treatment for GBS infections in pregnant women and newborns.GBS-positive pregnant women should be given the intervention treatment immediately to ensure the health of perinatal infants.

Evaluation of left ventricular rotation and twist by speckle tracking echocardiography in heart transplant recipients / 中华超声影像学杂志

Objective To evaluate the left ventricular rotation and twist in the cardiac allograft by speckle tracking echocardiography.Methods Twenty-six heart transplant recipients underwent echocardiographic studies at 1st,3rd,6th and 12th month after heart transplantation.Twenty-six healthy subjects served as controls.Parasternal basal and apical short-axis images of left ventricle were recorded and then were analyzed using EchoPAC software.The curves of basal and apical rotation and left ventricular twist were obtained,Peak values of basal and apical rotation and left ventricular twist were measured and then statistically analyzed.Results There were no significant differences in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) between heart transplant recipients and controls (P ＞0.05).The left ventricular twist,apical rotation were significantly lower in heart transplant recipients at 1 st,3rd,6th and 12th month after surgery than those in controls (P ＜0.05) ;while basal rotation in heart transplant recipients had no significant difference when compared with controls (P ＞0.05).The left ventricular twist,apical and basal rotation in heart transplant recipients among 1 st,3rd,6th and 12th month after surgery had no significant difference (P ＞ 0.05).Conclusions Although the LVEF and LVFS of cardiac allograft seemed normal,the left ventricular twist,apical rotation were still significantly lower in heart transplant recipients than those in controls.Speckle tracking echocardiography can be used for accurate assessment of left ventricular twist in heart transplant recipients.

A strain of extensively drug resistant and KPC-2 carbapenemase-producing Kleb-siella pneumoniae is identified in Dongguan,Guangdong province / 中国感染与化疗杂志

Objective To explore the extensively drug resistant mechanism and clinical treatment strategy of Klebsiella pneu-moniae .Methods The isolate was identified by Vitek2 Compact System.Antimicrobial susceptibility testing was conducted by Kirby-Bauer method.KPC-2 carbapenemase was detected by modified Hodge test.The gene encoding KPC-2 carbapenemase was amplified by polymerase chain reaction (PCR)and then sequenced.Results The strain was resistant to all antibiotics used in routine antimicrobial susceptibility testing except amikacin.Modified Hodge test showed positive result.KPC-2 gene was detected by PCR.The sequence was consistent with that of 11844849 in GenBank.After treatment for one month,no exten-sively drug resistant K.pneumoniae strain was detected from the patient.Conclusions It is necessary to strengthen the monito-ring and improve the awareness of extensively drug resistant K.pneumoniae for better control of such infections.