We aimed to investigate the underlying function and mechanism of E1231 against diabetic cardiomyopathy (DCM). H9c2 cells were exposed to either 33 mmol/L mannitol or an identical concentration of glucose (high glucose, HG) in vitro. In vivo, diabetes mellitus (DM) mice were induced by injection of 60 mg/kg streptozotocin intraperitoneally. E1231 was used to treat cells (5 mmol/L) or animals (40 mg/kg), and subsequent assays were conducted to determine its effect on DCM-associated manifestations. Western blot was employed to evaluate protein expressions of the silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). In vitro, treatment with E1231 significantly reduced oxidative stress and apoptosis induced by HG via activating the SIRT1-PGC-1α/Nrf2 pathway in H9c2 cells, compared to cardiomyocytes under HG conditions. In vivo, DM mice showed up-regulated SIRT1, PGC-1α, and Nrf2 expression, with protection against cardiac fibrosis, dysfunction, and oxidative stress impairment. The study demonstrated that E1231 alleviates cardiac dysfunction via activating the SIRT1-PGC-1α signaling pathway in DCM, leading to the activation of Nrf2. Therefore, E1231 has the potential to facilitate the treatment of DCM.

目的:探究4个炎症因子Toll样受体4(TLR4)、TNF受体相关因子6(TRAF6)、白细胞介素-6(IL-6)和白细胞介素-1β(IL4β)在深静脉血栓大鼠体内的表达及在深静脉血栓形成的作用.方法:将SD大鼠随机分成对照组(n=10)和模型组(n=90),采用血管钳夹结合固定制动的方式建立深静脉血栓模型,建模后分别于1h、6h、12h、1d、3d、7d、14d、21d、28d处死,检测血栓重量/长度比值、血浆中4个炎症因子的浓度,并进行组织学观察.结果:(1)1h、6h、12h的血栓重量/长度比值较低,组间无显著性差异(P＞0.05);1 d、3 d、7 d的血栓重量/长度比值维持在较高水平,组间无显著性差异(P＞0.05);14 d、21 d、28 d的血栓重量/长度比值均降低,组间无显著性差异(P＞0.05).(2)模型组中1-7 d的血栓重量/长度比值均明显高于正常组(P＜0.05).(3)模型组中1-7 d的TLR4、TRAF6、IL-6和IL-1β浓度水平均明显高于正常组(P＜0.05).(4)Pearson相关性分析显示TLR4、TRAF6、IL-6和IL-lβ浓度与血栓程度具有正相关性.结论:深静脉血栓大鼠体内的TLR4、TRAF6、IL-6和IL-1β表达上调可能在深静脉血栓形成中发挥了重要作用.

The abuse of antibiotics has enabled superbug and multi-drug resistant bacteria to cause significant harm to human health. A method for rapidly identifying and classifying antibiotic-resistant bacteria is required to avoid unreasonable antibiotic use. Here, we developed a rapid and culture-free bacteria detection method based on surface-enhanced Raman spectroscopy (SERS) of dual-enhanced silver nanoparticles. We demonstrated SERS detection of DNA, metabolites, cell wall components as well as discrimination of sensitive strains of S. aureus , E. coli , and several clinical pathogens. Notably, the SERS peak ratio was found to determine the inflexion point of accelerated bacterial death upon treatment with antibiotics. Our method is simple, rapid, and reproducible and is significant for rapidly classifying and identifying the pathogenic bacterium in 2 minutes. Our findings open up potentials to analyses drug resistance genes to guide clinical drug use by relevant SERS peaks, which can be extended easily to label-free sensing of cells and tissues in life sciences.

Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations. Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples. Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults. Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors.

Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China. Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter. To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China. Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections. Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus. Adenovirus positive samples were seeded onto A549 cells to isolate viral strains. Phylogenetic analysis was conducted on the highly variable region of adenoviral hexon gene. Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection. The co-infection rate in this study was 25.9% (49/189). The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus. Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137). Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally. Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Climate seasons could be rational indicators for the seasonality analysis of airborne viral infections. Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses.

OBJECTIVE To investigate antibiotic resistant profile of IRAB ,the epidemiology of OXA carbapene‐mase and ISAba1 in clinical isolates ,so as to provide the reference for rational use of antibiotics and control of nosocomial infections .METHODS Totally 140 strains of Acinetobacter baumannii isolated from Oct .2011 to Jun . 2012 in the hospital were collected .A multiplex PCR was designed to investigate the genotype of the ITS sequence of ABA .Antibiotic resistance was tested by K‐B method .Carbapenemase strains were primarily screened by the modified Hodges test .The OXA carbapenemase and integrase gene were determined by multiplex PCR .A single PCR was carried out to detect the ISAba1 upstream of blaOXA‐23‐like and blaOXA‐51‐like .Some positive strains of blaOXA‐23‐like ,blaOXA‐24‐like ,blaOXA‐51‐like were sequenced and gene determined by PCR .RESULTS Of 140 strains identified by multiplex PCR ,137 strains were ABA ,124 strains were IRBA and 13 were ISBA . The resistance rate of IRAB to most antibacterials was over 90 .00% .The gene detection rate of blaOXA‐51‐like , blaOXA‐23‐like were 91 .24% and 94 .89% respectively . No blaOXA‐58‐like gene was found . After whole genome sequencing ,the genotypes were OXA‐23 ,OXA‐72and OXA‐66 ,respectively .CONCLUSION ABA from Harbin region is seriously resistant to all the antibiotics ,and OXA‐23 is the major cause .ISAba1 plays an important role in the expression of OXA‐23 ..

Objective To detect, isolate and identify the type of adenovirus ( AdV) in sputum or throat swab specimens collected from respiratory infection patients who hospitalized in the Second Affiliated Hospital of Harbin Medical University.Methods The AdVs were prelimina-rily screened from the specimens by using direct immunofluorescence technique.The AdV posi-tive specimens were inoculated onto A549 cells and then further isolated and purified by using plaque assay methods.The nucleic acid sequences of adenoviral penton and hexon genes were amplified by PCR.The amplified PCR products were subject to sequence using Sanger’ s meth-od.The sequences were compared with the sequences of known penton and hexon genes in GenBank database by BLAST software to identify the exact type of adenovirus.Results One type of adenovirus was successfully separated from our specimens.The penton and hexon se-quences were 100%homological to those of human adenovirus type 7.Thus the isolated AdV strain was identifed as AdV type 7.Conclusion A strain of human respiratory adenovirus type 7 is successfully isolated from sputum specimens of patients in Harbin area.

Objective To isolate the adenovirus from clinical sample taken from a patient with respiratory tract infection and to identify the type of the isolated adenovirus. Methods One adenovirus positive sample from hospitalized patients with respiratory tract infection was seeded onto HeLa cell. Adenovirus strain was isolated and purified from the virus plaque assay. The hypervarible region of hexon gene was amplified by the extracted viral DNA via polymerase chain reaction( PCR). The PCR product was sequenced and the sequence was subjected alignment and basic local alignment search tool( BLAST) searching in GenBank. Results BLAST search analysis on Hexon gene showed that the adenovirus strain isolated was identical to human adenovirus type 3 strain USA / ak34_AdV3a2 with 100% homogeneity. Conclusion The adenovirus isolated from a clinical sample is identified as human adenovirus type 3.

We investigated the occurrence of AmpC beta-lactamases among Escherichia coli and Klebsiella pneumoniae isolates and determined the genotype of plasmid-mediated AmpC beta-lactamases at a medical center. The AmpC beta-lactamase promoter and attenuator were amplified from chromosomal DNA of high AmpC-producing E. coli isolates and sequenced. Antibiotic screening and 3D extract tests showed the presence of AmpC beta-lactamase in 3.56% of K. pneumoniae and 1.88% of E. coli isolates. Ten isolates (six K. pneumoniae and four E. coli) were positive for extended spectrum beta-lactamase (ESBL) as indicated by the double disc diffusion method. DHA-1 plasmid-encoded AmpC beta-lactamase was present in 10 K. pneumoniae isolates and four E.coli isolates. E. coli chromosomal AmpC beta-lactamase carried polymorphisms in the -42, -32, and -18 bases of the promoter and in the +26 and +27 bases of the attenuator, which may play a role in antibiotic resistance. The observed mutations may have clinical implications for the management of antibiotic-resistant infections.

Objective To investigate the etiological and epidemiological features of respiratory viral infection in hospitalized patients from Harbin region as a reference for clinical treatment and prevention of viral infections.Methods The nasopharyngeal aspirates samples were taken from 521 hospitalized patients with respiratory tract infection from August 2009 to September 2010.Seven kind respiratory viruses were screened using the fluresenant antibodies with direct immunofluorescence assay(DFA).Results Among all the 521 samples,74(14.2%) were respiratory virus positive.And among the 74 viral positive samples,single virus infection was 39 and more than one kind virus complex infection was 79 which accumulated as 118 viral infection.Among the 118 viral infections,respiratory syncytial virus accounted for 37.3%(44),adenovirus 5.1%(6),influenza virus A 31.4%(37),influenza virus B 7.6%(9),parainfluenzaⅠ16.2%(12),parainfluenzaⅡ0.8%(1),parainfluenza Ⅲ7.6%(9).The viral infection differences in season distribution were significant,and the differences in the others(age,gender and disease) were not significant.Conclusion RSV is dominant in respiratory infection,followed by influenza virus A.

>临床实验室全面质量管理的核心是质量控制,包括分析前、分析中、分析后质控三个方面。分析中和分析后质量控制主要在医学实验室中进行控制,已经建立起相对完善的管理体制,而分析前质量控制包括检验项目的选择、患者准备、标本采集、运送、实验室接收并处理标本等程序,涉及临床医生、护理人员、患者及临床实验室多个环节,影响因素众多,难以监测及控制,是实验室质量管理体系中的薄弱环节,据统计分析前误差占实验室总误差的一半以上。不合格标本的重新采集不仅会增加患者的痛苦,引起不必要的纠纷,还因标本的质量缺陷具有隐匿性而不易被实验室人员识别而导致错误的结果。护理人员是医嘱的直接执行者,负责患

Objective:To observe the expression level of microRNA-150 and collagen Ⅰ on myocardial fibrosis in diabetic rat model and myocardial fibroblasts,to discuss the influence of microRNA-150 on collagen Ⅰ in diabetes myocardial fibrosis.Methods: The diabetic rats were induced.The myocardial fibroblast were primary cultured.Masson staining and Elisa were used to detect collagen Ⅰ.Real-time PCR was used to detect microRNA-150.Results: The collagen Ⅰ level was higher in the DM group.The expression of microRNA-150 was downregulated in the DM group;Collagen Ⅰ of myocardial fibroblasts which were cultured in high glucose were downregulated after myocardial fibroblasts were transfected microRNA-150 micic.Conclusion: The microRNA-150 level can influence Collagen Ⅰ secretion in diabetes myocardial fibrosis,microRNA-150 might be involved in diabeties myocardial fibrosis.

<正>近年来,丝状真菌感染的发病率和死亡率不断上升,在侵袭性感染中,曲霉菌已成为临床上仅次于念珠菌的重要致病菌,其感染早期诊断目前还未引起足够重视。现就1岁幼儿烟曲霉菌感染的肺炎作一报道,望能引起临床医师及微生物检验人员的注意。哈尔滨医科大学附属第二医院检验科于

Objective:To explore the infection status and antibiotics resistance of non-fermenting bacteria in patients of intensive care unit,so as to guide rational application of antibiotics in clinic.Methods: The non-fermenting bacteria isolated from sputum of patients in intensive care unit in 2010 were identified and their drug sensitivity results were analyzed.Results: A total of 1047 strains of non-fermenting bacteria were isolated,performing the detection rate of 44%.The top three were Pseudomonas aeruginosa(50.13%),Acinetobacter baumannii(21.45%),Stenotrophomonas maltophilia(10.38%).They were high resistance to common antimicrobial agents.Conclusion: Non-fermenting bacteria isolated from hospitalized patients in intensive care unit show higher isolation rate and multidrug resistance.Therefore,pathogenic bacteria identification and antimicrobial susceptibility test should be strengthened to instruct antibiotics properly in clinic.

Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of γ-tocotrienol on tumor angiogenesis. The results showed that γ-tocotrienol (10-40 μmol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. γ-Tocotrienol (800-1200 μg/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of γ-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 μmol/L γ-tocotrienol. In addition, γ-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of β-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of γ-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing β-catenin expression. Thus, our results suggest that γ-tocotrienol has a potential chemopreventive agent via antiangiogenesis.

OBJECTIVE To investigate the clinical distribution and analyze of the antibiotic resistance of Pseudomnas aeruginosa to provide the basis for clinical medication.METHODS The isolated bacteria were identified by MicroScan WalkAway-96SI and the sensitivity test was performed by adopting Kirby-Bauer method,the data was analyzed by WHONET5.4 software.RESULTS 73.4% of P.aeruginosa were isolated from respiratory tract specimen gathered in ICU and neurosurgery department.Among the antibiotics,the resistance rate to cefoperazone/sulbactam was the lowest(15.7%),followed by amikacin(18.4%),imipenem(21.5%),piperacllin/tazobactam(26.6%) and ceftazidime(28.3%),but the resistant rate to cefazolin was the highest(100.0%).CONCLUSION P.aeruginosa is the major pathogenic bacteria in nosocomial infection.The surveillance to antimicrobial resistance is very important for guiding the rational application of antibiotics and controlling the prevalence of nosocomial infection.

Objective:To investigate the clincal distribution and analysis of the antibiotic resistance of infections caused by Enterobacter cloacae,provide the basis for clinical medication.Methods: Isolated colonies were identified by MicroScan WalkAway-96SI and sensitivity test adopted by Kirby-Bauer method,the data was analyzed by WHONET5.4 software.Results: Totally 103 strains of E.cloacae were mainly isolated from sample of sputum and urine and the rate were 50.5% and 18.4% respectively.E.cloacae was mainly distributed at departent of respiration and ICU.In the antiinfective drugs,the resistance rate to carbapenem was the lowest(0.00%),followed by amikancin,piperacllin/ tazobactam,cefoperazone/sulbactam,cefepime,levofloxacin(40.0%),it reflected highly resistance to ampicillin,cefazolin and cefoxitin(90.0%).Conclusion: The detection rate and drug resistance of E.cloacae are increasing severely.The surveillance of antimicrobial resistance is very important for guiding rational antimicrobial therapy to control hospital infection of E.cloacae.

Objective:To investigate the pathogens distribution and drug resistance of patients in intensive care unit and provide theoretical basis of rational usage of antibiotics for the clinic.Methods:Isolated colonies were identified by MicroScan-WalkAway96SI and sensitivity test abopted Kirby-Bauer method.Data was analyzed by WHONET5.4 software.Results:A total of 720 organisms were collected in the survey period,which included 476(66.1%)Gram-negative strains,175(24.3%) Gram-positive strains and 69(9.6%)fungal strains.Pseudomonas aeruginosa,Acinetobacter,Staphylococcus aureus,Coagulase negative Staphylococcus,and Klebsiella pneumonia were the most common isolates.Imipenem showed good antimicrobial activity against Gram-negative bacilli except stenotrophomonas maitophilia,and the resistances rate of three main Gram-positive coccus to Vancomycin was 0.00%.Conclusion:Monitoring of drug resistance to bacterium in ICU should be strengthened.Bacterial distribution,direct rational drug usage in the clinic can prevent bacterial strain of drug resistance from being transmitted.

Objective:To investigate the distribution of clinical fungus infection in order to analyze reasons,and causes more attention in clinical practice.Methods:Fungi were isolated by CHROMagar medium between 1-6 month in 2008.the fungi resistance to antifungal agents were examined including fluconazole,amphotericin B,itraconazole and flucytosine by Rosco disk diffusion method.Results:192 strains were identified,Candida albicans was the main species;they are distributed mainly among sputum and urine.All detected fungus show drug susceptibility to 4 antifungal drugs over 90% except itraconazole.Conclusion:Candida albicans,candidatropicalis and candida glabrata are the main microorganism at clinical fungal infections;antifungal drugs should be applied on the basis of drug susceptibility test to minimize fungus infection caused by the antibiotics,it would be beneficial to the proper clinical use of antibiotics.

Objective:To investigate the incidence of clindamycin-induced resistance in clinical strains of Staphylococcus and help clinical physicians select appropriate drugs.Methods:To detect the erythromcin and clindamycin resistance of Staphylococcus by K-B agar diffusion method and the clindamycin-induced resistance by D-test which is recommended by CLSI/NCCLS.Results:44.78% of MRSA and 13.94% of MRCNS in 232 stains Staphylococcus are resistant to erythromcin and clindamycin.18.53% of detected Staphylococcus are positive by D-test,and 52.43% of erythromcin resistant Staphylococcus are positive.In Staphylococcus aureus which are resistant to erythromcin and sensitive to clindamycin and Staphylococcus whose coagulase is negtive,the positive rate of D-test are 65.38% and 46.42% respectively.Conclusion:The rate of clindamycin-induced resistance is high in our hospital and physicians should keep an eye on it.