Table of Content

30 January 2019, Volume 34 Issue 1

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Clinical mass spectrometry：applications in clinical laboratories

Yan Victoria Zhang, Thomas Jackson

2019, 34(1):  1-7.  DOI: 10.3969/j.issn.1673-8640.2019.01.001

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Mass spectrometry has demonstrated great utility and potential in clinical applications due to its unique advantages over traditional methods. The current applications are categorized into 3 different instrument platforms and technologies,including tripe quadruple mass spectrometry,time-of-flight mass spectrometry（TOF-MS） and inductively coupled plasma mass spectrometry（ICP-MS）. This review is intended to provide an overview of determination items based on mass spectrometry in clinical laboratories and to focus on how technologies best support clinical needs. Furthermore,this review discusses the emerging applications of mass spectrometry in clinical laboratories to provide insights into the application of mass spectrometry in healthcare to better serve patient needs in the near future.

Analysis of the gene detection results of 6 545 cases of alpha-thalassemia

SHI Mingfang, YANG Lan, YU Xia, LIANG Xiuyun

2019, 34(1):  8-10.  DOI: 10.3969/j.issn.1673-8640.2019.01.002

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Objective To study the genotype characteristics of alpha-thalassemia in the population of Guangxi Nanning Jiangnan. Methods A total of 6 545 cases of suspected alpha-thalassemia and alpha-thalassemia carriers' spouses received gene detection,and the DNA was extracted and amplified in vitro. By gap polymerase chain reaction,4 common kinds of deficiency alpha-thalassemia genotypes （-α^3.7,-α^4.2,--SEA and --THAI）were detected. By reverse dot blot polymerase chain reaction,3 common kinds of non-deficiency alpha-thalassemia genotypes （HbCS,HbQS and HbWS） were detected. Results In the 6 545 cases,2 573 cases （39.31%） were identified with alpha-thalassemia gene. Among them,there were 1 083 cases （42.09%） of stationary type,1 370 cases （53.25%）of light type and 120 cases （4.66%） of intermediate type （hemoglobin H disease）. There were 2 070 cases of deficiency alpha-thalassemia,and the main genotypes were --SEA /αα,-α^3.7/αα and -α^4.2/αα. There were 77 cases of deficiency alpha-thalassemia with mutations,and the main genotypes were --SEA/α^WSα,--SEA/α^CSα and -α^3.7/α^WSα. There were 426 cases of non-deficiency alpha-thalassemia,and the main genotypes were α^CSα/αα,α^WSα/αα and α^QSα/αα. Conclusions There are many carriers of alpha-thalassemia gene in Guangxi Nanning Jiangnan. The main genotypes of deficiency and non-deficiency alpha-thalassemia are --SEA/αα and α^CSα/αα,respectively. There are many cases of intermediate type alpha-thalassemia（hemoglobin H disease） as well. It should perform gene screening and detection at local area.

Correlation between high-sensitivity cardiac troponin T and the characteristics of coronary atherosclerosis

WANG Kaijuan, LI Tiewei, WANG Zongjian, CHEN Xi, GAO Xiaojing, LIN Yahui, ZHOU Zhou, KANG Jinsuo

2019, 34(1):  11-18.  DOI: 10.3969/j.issn.1673-8640.2019.01.003

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Objective To evaluate the correlation between high-sensitivity cardiac troponin （hs-cTn）T and the severity of coronary atherosclerosis according the results of medical imaging. Methods A total of 436 patients with suspected coronary atherosclerosis disease（CAD） and undergoing coronary computed tomography （CT） were enrolled. There were 222 cases of CAD（CAD group）and 214 cases of non-CAD（control group）. Serum hs-cTnT,blood glucose （Glu）,blood urea nitrogen（BUN）,creatinine （Cr） and uric acid（UA） levels were determined,and estimated glomerular filtration rate （eGFR） was calculated. The correlation between hs-cTnT and the severity of coronary atherosclerosis was analyzed from 3 aspects,including the number of stenosed vessels,the degree of stenosis and the vulnerability of plaques. All subjects were classified according to hs-cTnT quartile distribution （Q1,Q2,Q3 and Q4 from low to high）. The percentages of patients with stenosed vessels,stenosis and plaques in Q1-Q4 were compared. Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation of these indicators. Logistic regression analysis was used for multivariate analysis. Results Hs-cTnT,coronary artery calcification score （CACS）,Glu and UA increased with the increasing number of stenosed vessels （P<0.05）,while eGFR decreased（P<0.05）. Hs-cTnT,CACS,Glu,UA,Cr and BUN increased with the degree of stenosis （P<0.05）. Pearson correlation analysis showed that hs-cTnT was positively correlated with BUN,Cr,UA and Glu（r=0.312,0.239,0.134 and 0.131,respectively,P<0.05）. The quartile distribution of hs-cTnT was positively correlated with the number of stenosed vessels,the degree of stenosis and ts in Q1 decreased. After adjusting for traditional risk factors （age,sex,hypertension,diabetes mellitus,smoking and drinking） and renal function indhe vulnerability of plaques（r_s=0.249,0.252 and 0.239,respectively,P<0.01）. The percentages in Q1-Q4 had statistical significance with those in control group （P<0.05）. With the increasing number of stenosed vessels,the degree of stenosis and the vulnerability of plaques,the percentages in Q4 increased,while the percentageices （BUN,Cr,UA and eGFR）,hs-cTnT could not be an independent predictive factor for coronary atherosclerosis. Conclusions Although hs-cTnT is closely correlated with the severity of coronary atherosclerosis,but it is also affected by sex,age,renal function and other underlying diseases,so it can not be an independent predictive factor for coronary atherosclerosis.

Role of small and dense low-density lipoprotein cholesterol in cardiovascular and cerebrovascular diseases

WANG Shengkui, ZHOU Jun

2019, 34(1):  19-22.  DOI: 10.3969/j.issn.1673-8640.2019.01.04

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Objective To investigate the role of small and dense low-density lipoprotein cholesterol （sd-LDL-C） in 4 kinds of cardiovascular and cerebrovascular diseases [coronary heart disease,type 2 diabetes mellitus（T2DM）,hypertension and cerebral stroke]. Methods A total of 50 patients with hypertension,90 patients with T2DM,129 patients with coronary heart disease and 110 patients with cerebral stroke were enrolled as disease group. Totally,104 healthy subjects were enrolled as healthy control group. The levels of blood glucose （Glu）, apolipoprotein A1（apo A1）,apolipoprotein B（apo B）,apolipoprotein E（apo E）, total cholesterol（TC）,triglyceride（TG）,homocysteine（Hcy）,high-density lipoprotein cholesterol（HDL-C）,low-density lipoprotein cholesterol（LDL-C） and sd-LDL-C were determined in disease and control groups. The relationship was evaluated by Spearman correlation analysis. Results The apo B,TC,Glu and sd-LDL-C levels in hypertension group were higher than those in control group （P<0.05）. The TG and Hcy levels in cerebral stroke group were higher than those in control group （P<0.05）,and the apo A1,apo B,apo E and LDL-C levels were lower （P<0.05）. The TC,Glu,TG,Hcy and sd-LDL-C levels in T2DM group were higher than those in control group （P<0.05）,and the apo A1 level was lower （P<0.05）. The TC,Glu,TG and Hcy levels of coronary heart disease group were higher than those in control group （P<0.05）,and the apo A1 level was lower than that in control group （P<0.05）. The sd-LDL-C level in coronary heart disease group was positively correlated with apo A1,apo B,apo E,TC and LDL-C （r=0.372,0.316,0.248,0.718 and 0.316,P<0.05）,and it was negatively correlated with HDL-C（r=-0.218,P<0.05）. The sd-LDL-C level in T2DM group was positively correlated with apo A1,apo B,apo E,TC,TG and LDL-C（r=0.243,0.779,0.416,0.616,0.614 and 0.678,P<0.05）. The sd-LDL-C level in hypertension group was positively correlated with TC,TG and LDL-C（r=0.623,0.756 and 0.699,P<0.05）,and it was negatively correlated with HDL-C（r=-0.355,P<0.05）. The sd-LDL-C level in cerebral stroke group was positively correlated with apo A1,apo E and TG（r=0.398,0.117 and 0.271,P<0.05）. Conclusions Sd-LDL-C levels in T2DM and hypertension groups are increased,and the level of sd-LDL-C plays a role in cardiovascular and cerebrovascular diseases.

Changes of serum hepcidin levels in postmenopausal women with osteoporosis

YANG Juan, XU Jin

2019, 34(1):  23-27.  DOI: 10.3969/j.issn.1673-8640.2019.01.005

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Objective To investigate the correlations of serum hepcidin levels with bone metabolism indices and bone mineral density（BMD） in postmenopausal women with osteoporosis. Methods A total of 106 postmenopausal women with osteoporosis and 92 postmenopausal women without osteoporosis were enrolled. According to BMD,they were classified into osteoporosis group（106 cases）,bone mass reduction group（57 cases） and bone mass normal group（35 cases）. Their clinical data were collected. BMD was determined. Serum levels of hepcidin and bone metabolism indices [procollagen Ⅰ N-terminal peptide（PⅠNP）,osteopontin（OPN）,beta degradation product of carboxylterminal telopeptide of type Ⅰ collagen（β-CTX） and N-terminal osteocalcin（OC）] were determined. Receiver operating characteristic（ROC） curve was used to analyze the role of serum hepcidin in the diagnosis of osteoporosis. Pearson correlation analysis and partial correlation analysis were used to evaluate the correlations. Results Serum levels of hepcidin,lumbar BMD and femoral neck BMD in osteoporosis group were lower than those in bone mass reduction group and bone mass normal group（P<0.05）,and those in bone mass reduction group were lower than those in bone mass normal group（P<0.05）. Serum levels of PⅠNP,OPN,β-CTX and OC in osteoporosis group were higher than those in bone mass reduction group and bone mass normal group（P<0.05）,and serum levels of PⅠNP,OPN and β-CTX in bone mass reduction group were higher than those in bone mass normal group（P<0.05）. ROC curve analysis showed that the area under curve（AUC） of serum hepcidin in the diagnosis of osteoporosis for postmenopausal women was 0.780,the optimal cut-off value was 35.0 μg/L,the sensitivity was 91.5%,and the specificity was 57.6%. Pearson correlation analysis showed that serum level of hepcidin was negatively correlated with age,PⅠNP,OPN,β-CTX and OC（P<0.05）,while it was positively correlated with weight,lumbar BMD and femoral neck BMD（P<0.05）. Partial correlation analysis showed that whether age was corrected,or age and weight were corrected,serum level of hepcidin was negatively correlated with PⅠNP and OPN（P<0.05）,while it was positively correlated with lumbar BMD and femoral neck BMD（P<0.05）. Conclusions Serum level of hepcidin in postmenopausal women with osteoporosis is decreased,and it is related with age,bone metabolism indices and BMD.

Expressions of IL-17,IL-22 and IL-10 in peripheral blood mononuclear cells in children with bronchial asthma

LU Guanghui, CHU Zhihua, ZHOU Fawei, YANG Nianan, YANG Jie, WANG Jiaoping, ZENG Shoukui

2019, 34(1):  28-32.  DOI: 10.3969/j.issn.1673-8640.2019.01.006

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Objective To investigate the expressions of interleukin （IL）-17,IL-22 and IL-10 in peripheral blood mononuclear cells in children with bronchial asthma. Methods A total of 75 children with asthma were classified into exacerbation group （41 cases） and remission group （34 cases）. A total of 40 healthy children were enrolled as control group. The peripheral blood mononuclear cells were isolated. The expressions of IL-17,IL-22 and IL-10 genes in peripheral blood mononuclear cells were determined by real-time quantitation polymerase chain reaction （PCR）. The expressions of IL-17,IL-22 and IL-10 proteins in peripheral blood mononuclear cells were determined by western blotting. The forced expiratory volume in 1 second （FEV1） and the ratio of FEV1/forced vital capacity （FVC） were determined. The correlations among the variables were analyzed by Pearson correlation analysis. Results The FEV1 and FEV1/FVC in exacerbation group were lower than those in remission group and control group （P<0.05）,and those in remission group were lower than those in control group（P<0.05）. The relative expression levels of IL-17 mRNA and IL-22 mRNA in peripheral blood mononuclear cells in exacerbation group were higher than those in remission group and control group （P<0.05）,and those in remission group were higher than those in control group （P<0.05）. However, the relative expression level of IL-10 mRNA was lower than those in remission group and control group （P<0.05）,and that in remission group was lower than that in control group （P<0.05）. The relative expression levels of IL-17 mRNA, IL-17 protein and IL-22 mRNA, IL-22 protein in peripheral blood mononuclear cells in asthmatic children were negatively correlated with the relative expression levels of IL-10 mRNA and IL-10 protein,FEV1 and FEV1/FVC（P<0.05）,and the relative expression levels of IL-10 mRNA and IL- 10 protein were positively correlated with FEV1 and FEV1/FVC （P<0.05）. Conclusions The expressions of IL-17 and IL-22 in peripheral blood mononuclear cells of children with asthma are upregulated,while the expression of IL- 10 is downregulated,which are related with disease status. It prompts that T helper cell 17（Th17）/regulatory T cell （Treg） imbalance might be involved in the pathogenesis of asthma.

Drug resistance of methicillin-resistant Staphylococcus aureus to mupirocin,fusidic acid and retapamulin

CHEN Wenjing, HE Chunyan, YANG Han, ZHAO Huanqiang, CUI Zelin, TANG Rong, LIU Qingzhong

2019, 34(1):  33-37.  DOI: 10.3969/j.issn.1673-8640.2019.01.007

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Objective To investigate the drug resistance of methicillin-resistant Staphylococcus aureus （MRSA） to mupirocin,fusidic acid and retapamulin. Methods A total of 1 037 MRSA isolates were collected. The minimum inhibitory concentrations （MIC） of mupirocin,fusidic acid and retapamulin were determined by microbroth dilution method. The isolates resistant to 3 antibiotics were screened. The drug resistance of MRSA to mupirocin,fusidic acid and retapamulin was determined by Vitek 2 Compact analyzer. Results Among the 1 037 MRSA isolates,54 （5.2%） MRSA isolates were resistant to mupirocin,and 85.2% of them were high-level mupirocin resistance（MuH）. Among 9 （0.9%） fusidic acid resistant MRSA isolates,77.8% of them were low-level fusidic acid resistance（FAL）. The proportion of retapamulin resistant MRSA isolates was the lowest （0.2%）. The MRSA isolates,which were resistant to mupirocin,fusidic acid and retapamulin,were also highly resistant to aminoglycosides,macrolides,lincosamides and fluoroquinolones. Conclusions Low mupirocin,fusidic acid and retapamulin resistance in MRSA isolates is found. The existence of a small amount of drug resistant isolates suggests that it should strengthen the determination and surveillance of the drug resistance of Staphylococcus aureus.

Serum galactomannan antigen and Aspergillus fumigatus antibodies in the diagnosis of invasive pulmonary aspergillosis

ZHANG Wei, SHEN Ling

2019, 34(1):  38-41.  DOI: 10.3969/j.issn.1673-8640.2019.01.008

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Objective To investigate the roles of serum galactomannan （GM） antigen and Aspergillus fumigatus antibodies in the diagnosis of invasive pulmonary aspergillosis （IPA）. Methods A total of 124 patients with suspected IPA were enrolled and classified into IPA group （46 cases） and non-IPA group （78 cases）. Serum GM antigen and Aspergillus fumigatus IgG and IgM antibodies were determined,and the clinical data were analyzed retrospectively. Results There were 18 cases confirmed by pathological examinations and 28 cases confirmed by clinical diagnosis in IPA group. When the cut-off values of GM were 0.5 and 1.0 ng/mL,the sensitivities were 58.7% and 50.0%,and the specificities were 74.4% and 83.3%,respectively. The sensitivity and specificity of Aspergillus fumigatus IgG antibody were 80.4% and 91.0%,and those of Aspergillus fumigatus IgM antibody were 71.7% and 87.2%. The levels of IgG and IgM in IPA group were higher than those in non-IPA group （P<0.05）. Conclusions Serological tests have high specificities （>80%） in the diagnosis of IPA,especially GM antigen （the cut-off value of GM is 1.0 ng/mL）and Aspergillus fumigatus IgG and IgM antibodies. The sensitivity and specificity of Aspergillus fumigatus IgG antibody are better than those of Aspergillus fumigatus IgM antibody．

Influence of neonatal blood sample hemolysis on the determination of serum neuron-specific enolase and establishment of correction equation

WANG Qiang, LU Xiaolan, WANG Guangrong, CAI Yanjuan, DU Qin, ZHANG Maoxin, ZHANG Guoyuan, WANG Dongsheng

2019, 34(1):  42-46.  DOI: 10.3969/j.issn.1673-8640.2019.01.009

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Objective To evaluate the influence of neonatal blood sample hemolysis on the determination of serum neuron-specific enolase（NSE）,and to establish correction equation. Methods Chemiluminescence was used to determine the change of serum NSE level before and after adding self-frozen thawed red blood cells in 72 neonates borned less than 24 h. The changes of hemoglobin（Hb） before and after adding were determined by cyanmethemoglobin（HiCN）. The correction equation was established. The feasibility of correction equation was evaluated by comparing the NSE results with the NSE results corrected by self-constant and the correction equation. The NSE correction equation for instrumental method was established by analyzing the correlation of Hb results determined by HiCN method and instrumental method. Results The change constants of NSE in 72 neonates with serum hemolysis was（23.70 ±3.62） mg/g Hb. The relationship of concentration variation between Hb and NSE in neonatal bloodsample was ΔNSE_serum=23.17×ΔHb_HiCN （Y=23.17X,r²=0.812 2,P<0.001）. There was no statistical significance of NSE corrected results between self-constant group and correction equation group（P=0.541）. The linearity for Hb of instrumental method with HiCN was high（r²=0.992 4,P<0.001）. The correction equations of NSE in neonatal hemolytic serum were NSE_correction=NSE_measurement-23.17Hb_HiCN and NSE_correction=NSE_measurement-23.60Hb_instrument+13.22. Conclusions Hemolysis has a serious influence on the determination of NSE in serum. For neonatal hemolytic sera,it is critical to evaluate the severity of neonatal hypoxic ischemic encephalopathy by correcting NSE level.

Performance evaluation of different homocysteine determination systems

LIN Feiran, LIU Wenbin, OU Yuanzhu, YU Xiaoxuan, GE Danhong, TANG Liping

2019, 34(1):  51-55.  DOI: 10.3969/j.issn.1673-8640.2019.01.011

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Objective To evaluate the performance of 11 commercial cycle enzymatic assay reagents for homocysteine（Hcy） determination. Methods Hcy cycle enzymatic assay reagents from 11 manufacturers were selected,and they were combined with HITACHI 7180 automatic analyzer to set up 11 determination systems respectively. According to the Clinical and Laboratory Standards Institute（CLSI） EP15-A2 and EP6-A documents and the standard of YY/T 1258—2015,the within-laboratory precisionns,truenesses and linearities of 11 determination systems and between-run variations from 9 determination systems were verified. Results The precisions of 11 determination systems met the requirements [<1/3 standard of external quality assessment （EQA） （6.67%）]. Except the between-run variations for middle-level and high-level samples in 1 determination system was out of range （>10.00%,1/2 standard of EQA）,the between-run variations of the other determination systems were <10%. The truenesses of 4 determination systems were not within the verification limit of accuracy,and there were 3 determination systems with nonlinear results through linear range verification. Conclusions For Hcy determination,performance differences exist among the 11 determination systems. Performance evaluation should be performed before Hcy determination in clinical laboratories.

Preliminary application of visual LAMP in detecting drug resistant gene bla_KPC-2 of carbapenem resistant Klebsiella pneumoniae

ZOU Ping, BAO Junfeng, ZANG Jia, ZHANG Ting, XU Yaohui

2019, 34(1):  56-59.  DOI: 10.3969/j.issn.1673-8640.2019.01.012

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Objective To establish a method for detecting drug resistant gene bla_KPC-2 of carbapenem resistant Klebsiella pneumoniae by visual loop-mediated isothermal amplification （LAMP）. Methods A total of 3 pairs of specific LAMP primers were designed,and the LAMP detection system of 25 μL was established and optimized. The specificity and sensitivity were compared with those of polymerase chain reaction （PCR）. Results A method for detecting drug resistant gene bla_KPC-2 of carbapenem resistant Klebsiella pneumoniae by visual LAMP was established,which was used in the rapid detection of bla_KPC-2 at 63 ℃ for 40 min. The specificity was close to that of PCR,and the sensitivity was higher than that of PCR for 10 times. There were 12 isolates detected with bla_KPC-2 by LAMP among 25 imipenem,meropenem or ertapenem resistant isolates,and there were 5 isolates detected with bla_KPC-2 by LAMP among 31 imipenem,meropenem and ertapenem resistant isolates（P=0.009 9）. Conclusions The established LAMP could be used as a method to detect bla_KPC-2,but it could not replace drug susceptibility test in vitro.

Hippo/YAP signaling pathway regulation protein ACAN as a new serum tumor marker for hepatocellular carcinoma

SHANG Lu, ZHAO Xiao, CHEN Yan, WU Qi, ZHU Guoqing, LIU Ya, WANG Jiayi, SUN Fenyong, ZHANG Lei

2019, 34(1):  60-66.  DOI: 10.3969/j.issn.1673-8640.2019.01.013

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Objective To investigate the role of Hippo/Yes related protein（YAP） signaling pathway regulation protein aggrecan（ACAN）in the diagnosis of hepatocellular carcinoma （HCC）. Methods A total of 156 HCC patients,33 hepatitis B patients,31 hepatitis C patients,30 liver cirrhosis patients,26 colon cancer patients,19 lung cancer patients,22 gastric cancer patients,20 breast cancer patients and 100 healthy subjects （healthy control group） were enrolled. Their ACAN levels were determined. YAP over-expressive vector and YAP-shRNA lentivirus plasmid were used to transfect hepatoma cell lines Bel-7402 and SMMC-7721. Over-expressive cAMP-response element binding protein （CREB）,TEA domain family member（TEAD）,alpha-globin transcription factor CP2（TFCP2）,Runt-related transcription factor 2 （RUNX2）vectors were individually transfected and co-transfected with YAP into Bel-7402 and SMMC-7721 cells,respectively. The expression of ACAN mRNA and the effects of different vectors on ACAN wild and mutant type promoters were determined. The diagnostic efficiency of ACAN and alpha-fetoprotein（AFP） for the diagnosis of HCC was evaluated. Results The levels of ACAN in HCC group were higher than those in gastric cancer,colon cancer,breast cancer,lung cancer,hepatitis B,hepatitis C and healthy control groups （P=0.000）,but there was no statistical significance among the other groups （P>0.05）. The expression of ACAN mRNA increased after the over-expression of YAP（P<0.01）,but it decreased after YAP knockout （P<0.01）. Compared with other transcription factors （TEAD,TFCP2 and RUNX2）,over-expressive CREB and co-transfected CREB and YAP could promote the expression of ACAN mRNA （P<0.01）. The wild type ACAN promoter can be affected by CREB and YAP,while the mutant type ACAN promoter was not affected. There was a positive correlation between ACAN and AFP,alanine aminotransferase （ALT）and aspartate aminotransferase （AST）（r=0.722,0.517 and 0.443,P=0.000）. Receiver operating characteristic （ROC） curve showed that the areas under the curves （AUC）of ACAN and AFP were 0.978 and 0.661. The AUC of ACAN were 0.903 and 0.993 for the diagnosis of stage Ⅰ-Ⅱ and stage Ⅲ HCC,respectively. Conclusions The diagnostic efficiency of ACAN for HCC is better than that of AFP. The diagnostic efficiency for advanced HCC is superior to that of early HCC. ACAN can be used as a new tumor marker for the diagnosis of HCC and plays a role through Hippo/YAP signaling pathway.

Drug resistance mechanism of carbapenem resistant Providencia rettgeri carrying bla_NDM-1

LI Wei, AI Fuqi, MA Yimin, WANG Bei, TIAN Yueru

2019, 34(1):  67-70.  DOI: 10.3969/j.issn.1673-8640.2019.01.014

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Objective To investigate the phenotype,mechanism,disseminative way and homology of carbapenem resistant Providencia rettgeri. Methods A total of 17 isolates of Providencia rettgeri isolated from intensive care unit （ICU） were collected,and antibiotic susceptibility test,drug resistance gene detection,NP test,pulsed-field gel electrophoresis （PFGE）,plasmid mobility analysis and replicon typing were performed. Results The 17 isolates of carbapenem resistant Providencia rettgeri carried bla_NDM-1. The drug resistance rates to ertapenem,meropenem,imipenem,cefazolin,cefuroxime,cefotaxime,cefepime,cefmetazole,piperacillin,trimethoprim-sulfamethoxazole,amikacin,gentamicin,tobramycin,kanamycin,ciprofloxacin and furadantin were 100.00%. The drug resistance rates to piperacillin-tazobactam and aztreonam were 88.23%. PFGE homology analysis showed that 15 isolates were the main epidemic isolates in ICU. Plasmid analysis showed that the bla_NDM-1 were located on conjugative plasmid （-160 kb）,and replicon type was type A/C. Plasmid carried a variety of drug resistance genes,being sensitive to ciprofloxacin and furadantin,and it mediated the high-level drug resistance to carbapenems,cephalosporins,cephamycins,sulfonamides and aminoglycosides. Conclusions Providencia rettgeri carrying bla_NDM-1 shows multi-drug resistance to common antibiotics,and it brings challenge to clinical anti-infection treatment.

Clinical experimental research progress of primary glaucoma pathogenesis

MA Yi, CAO Wenjun, SUN Xinghuai

2019, 34(1):  71-75.  DOI: 10.3969/j.issn.1673-8640.2019.01.015

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Glaucoma is a leading cause of irreversible vision loss in the world. Because it may be asymptomatic until the patients are at a relatively late stage and undergo characteristic glaucomatous optic neuropathy,the diagnosis is frequently delayed. Although the pathogenesis of primary glaucoma is complex and diverse,several important pathomechanisms related to primary glaucoma have been discovered,involving mechanical compression,vascular structural and functional damage,oxidative stress,inflammation and immune dysregulation. The research of the key pathways and molecules has made progress. Clinical experimental studies have also identified many candidate biomarker clusters that are potential targets for clinical diagnosis and treatment through further research. This review focuses on the progress of clinical experimental research in the pathogenesis of primary glaucoma to provide a reference for further clinical studies.

Research progress of VAP in determining plasma lipoprotein subfractions

LIANG Chunzi, ZHU Man, TU Jiancheng

2019, 34(1):  76-81.  DOI: 10.3969/j.issn.1673-8640.2019.01.016

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More evidence is accentuating the special subfractions of plasma lipoproteins,including remnant-like lipoprotein particles（RLP）,lipoproteins （a） [Lp（a）],high-density lipoprotein （HDL） subfractions （HDL2 and HDL 3） and particle concentration,like small density low-density lipoprotein particle （sd-LDL-P）, in the progression of cardiovascular disease（CVD）. The changes of pattern and number of these indicators are closely related to CVD risk and treatment strategy. Vertical auto profile （VAP） refers to the classical principle of ultracentrifuge lipid determination,which can effectively realize complete separation of plasma lipoprotein particles. After the comprehensive analysis of lipoprotein internal cholesterol level,volume,density and particle pattern,VAP provides comprehensive blood lipid data for the early screening and risk evaluation of related diseases,making up for the gaps in traditional blood lipid programs. VAP has accumulated a large amount of scientific researches and clinical data in North America over the past 20 years. This review briefly introduces its characteristics in plasma lipoprotein subfractions and particle determination and presents new progress of its application in CVD risk management.