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.

Non-alcoholic fatty liver disease(NAFLD) has become the main cause of chronic liver disease in children worldwide, and the incidence of NAFLD shows an increasing trend year by year. The risk factors leading to the onset of NAFLD in children are diversified and different from those in adults. At present, most medical institutions still pay little attention to NAFLD in children. This paper summarizes the risk factors and mechanisms for NAFLD in children, including gene polymorphism, maternal and fetal conditions, diet and living habits, environmental exposure, metabolic syndrome, endocrine-related mechanisms and intestinal microecology, in order to provide reference for the prevention and management of childhood NAFLD.

OBJECTIVE To systematically review the background of bioequivalence assessment of nasal sprays and nasal aerosols and the guiding considerations for the bioequivalence assessment of these complex drug-device combination products by regulatory authorities in the United States, the European Union(EU) and China. METHODS This article provided detailed explanations on the innovative weight of evidence assessment approach adopted by the US Food and Drug Administration(FDA), and the statistical rationale, methods and considerations for the bioequivalence assessment of nasal sprays and nasal aerosols. Using the calculation methods described in the draft guidance for budesonide inhalation suspension and the draft guidance for fluticasone nasal spray propionate issued by FDA, the statistical parameters of two-sided and one-sided population bioequivalence calculation were realized through R language programming, and pseudo-code for the population bioequivalence (PBE) calculation programs was provided. This article also presented a comprehensive review of published guidelines and summaries review principles of the EU and China for nasal sprays and nasal aerosols equivalence assessment. RESULTS & CONCLUSION Nasal sprays/nasal aerosols is the focus of innovative and generic drug development in recent years. This paper provided valuable considerations references for the research and development, quality control and bioequivalence evaluation of generic preparations of nasal sprays/nasal aerosols.

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals of humans because of its high fucoxanthin(Fx)content.However,multi-omics analysis of the regula-tory networks for Fx biosynthesis in I.galbana has not been reported.In this study,we report a high-quality genome assembly of I.galbana LG007,which has a genome size of 92.73 Mb,with a contig N50 of 6.99 Mb and 14,900 protein-coding genes.Phylogenetic analysis confirmed the monophyly of Haptophyta,with I.galbana sister to Emiliania huxleyi and Chrysochromulina tobinii.Evolutionary analysis revealed an estimated divergence time between I.galbana and E.huxleyi of～133 million years ago.Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion,including IgPLMT,IgOAR1,and IgDEGS1.Metabolome analysis showed that the content of carotenoids in I.galbana cultured under green light for 7 days was higher than that under white light,and β-carotene was the main carotenoid,accounting for 79.09％of the total carotenoids.Comprehensive multi-omics analysis revealed that the content of β-carotene,antheraxanthin,zeaxanthin,and Fx was increased by green light induction,which was significantly correlated with the expression of IgMYB98,IgZDS,IgPDS,IgLHCX2,IgZEP,IgLCYb,and IgNSY.These findings contribute to the understanding of Fx biosynthesis and its regulation,pro-viding a valuable reference for food and pharmaceutical applications.

Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.

In this study, we aimed to (1) identify white matter (WM) deficits underlying the consciousness level in patients with disorders of consciousness (DOCs) using diffusion tensor imaging (DTI), and (2) evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest (ROIs), and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.
Adult ; Brain Stem ; diagnostic imaging ; Consciousness ; physiology ; Consciousness Disorders ; diagnostic imaging ; pathology ; Diffusion Tensor Imaging ; methods ; Female ; Humans ; Image Processing, Computer-Assisted ; methods ; Male ; Middle Aged ; White Matter ; pathology ; physiopathology

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.

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.

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.

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.