Ischemic Postconditioning Attenuates Myocardial Ischemia-Reperfusion-Induced Acute Lung Injury by Regulating Endoplasmic Reticulum Stress-Mediated Apoptosis

ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.

Research progress of solute carriers related genes in malignant tumors / 国际肿瘤学杂志

As a transport channel for amino acids, solute carrier (SLC) exists in all kinds of cells, and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years, SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors, which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors, and their expression is closely related to the growth, metastasis, treatment and prognosis of tumor cells. Moreover, the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors, the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.

Analysis on drug transporters-mediated interaction between drugs and metformin / 中国基层医药

Objective:To investigate the potential drug interactions of outpatient prescriptions containing metformin combined with other drugs from the perspective of drug transporters.Methods:The prescriptions containing metformin that were used in the Outpatient Department of Hainan General Hospital, China between July and December 2019 were collected. The potential interaction between drugs and metformin used in the prescriptions was analyzed according to drug instructions, Drugbank, PubMed databases.Results:A total of 15 568 outpatient prescriptions containing metformin were collected, including 9 146 prescriptions for male patients and 6 422 prescriptions for female patients. A total of 14 902 prescriptions contained combined medication. The drugs used in combination included other hypoglycemic drugs, antiplatelet drugs, antihypertensive drugs, lipid-lowering drugs, and neuroprotective drugs. The drug transporters including aspirin, atorvastatin calcium, repaglinide, bisoprolol, metoprolol and clopidogrel had a potential interaction with metformin. There were 11 614 prescriptions containing drug transporters and metformin, including 5 938 prescriptions inhibiting organic cation transporter 1 and 5676 prescriptions inhibiting organic cation transporter 2.Conclusion:There is no incompatibility between the outpatient prescriptions containing metformin and the commonly used drugs for chronic diseases, but the outpatient doctors do not have enough knowledge about dose adjustment caused by potential interaction.

Expressions and significances of miR-135a-5p and TXNIP in papillary thyroid cancer / 中国医师杂志

Objective To detect the expression of miR-135a-5p and thioredoxin interaction protein (TXNIP) in papillary thyroid carcinoma (PTC) and to analyze their clinical significances.Methods 48 patients with PTC who underwent operation and confirmed by pathological examination in Shandong Provincial Third Hospital from March 2017 to March 2018 were selected.Tumor tissues and adjacent tissues were collected.The expression of TXNIP protein was detected by streptavidin peroxidase (SP) and Western blot,and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-135a-5p.Results The positive expression rate of TXNIP protein in adjacent tissues of PTC patients was significantly higher than that in tumor tissues (P ＜ 0.05);the expression level of TXNIP protein in tumor tissues of PTC patients was significantly lower than that in adjacent tissues (P ＜ 0.05);the expression of miR-135a-5p in PTC patients was significantly lower than that in adjacent tissues (P ＜ 0.05);in patients with PTC tumor diameter (≥2 cm) and lymph node metastasis,the proportion of patients with low expression of miR-135a-5p was significantly higher than those with high expression of miR-135a-5p(P ＜0.05);in patients with PTC tumor diameter (≥2 em) and lymph node metastasis,the proportion of patients with negative TXNIP expression was significantly higher than that of patients with positive TXNIP expression (P ＜0.05);there was a significant positive correlation between the expression of miR-135a-5p and TXNIP in PTC patients (P ＜ 0.05).Conclusions The expression levels of miR-135a-5p and TXNIP in tumor tissues of PTC patients are lower than those in adjacent tissues.The expression levels of miR-135a-5p and TXNIP were positively correlated with the increase of tumor diameter and lymph node metastasis.The low expression of miR-135a-5p and TXNIP may be related to the occurrence and deterioration of PTC tumors.

Diagnositic value of urine heparin-binding protein, interleukin-6 and white blood cell in bacterial urinary tract infection / 中华检验医学杂志

Objective To evaluate the diagnostic values of urinary heparin-binding protein (HBP), interleukin-6 (IL-6) and white blood cell (WBC) levels in bacterial urinary tract infection (UTI). Methods A case-control method was used. Urine of 157 cases of bacterial UTI, 61 cases of non-infection, and 40 cases of normal controls were collected in the Third Xiangya Hospital of Central South University from September 2017 to March 2018. U-HBP levels were measured in duplicate using a commercial HBP ELISA, U-IL-6 concentrations were analyzed with an up-conversion luminescence. The method of quantitative culture of bacteria was used to identify pathogenic species. Rapid dipstick tests and urinary sediment analyses were detected by FUS-2000 Urinalysis Hybrid. For continuous variables with skewed distributions, comparisons among the three groups were performed using the nonparametric Kruskal-Wallis test, and Mann-Whitney U test was used to further evaluate the difference between two groups. The Chi-square test was applied to analyze dichotomous. Receiver operating characteristic curve (ROC curve) was constructed to analyze the clinical diagnostic values of U-HBP, U-IL-6 and U-WBC for bacterial UTI. Results The levels of U-HBP in UTI group, non-UTI group and control group were 513.43 (50.45-644.40) ng/ml, 55.65 (20.43-314.55) ng/ml and 4.83 (3.28-12.63) ng/ml. The scores of U-IL-6 were 5.72 (3.84-9.02) pg/ml, 5.31 (4.31-6.39) pg/ml and 5.06 (4.56-6.18) pg/ml. The scores of U-WBC were 205 (24-754) cells/μl, 34 (13-117) cells/μl and 0 (0-0) cell/μl. There were statistically significant differences of U-HBP and U-WBC among the three groups (HU-HBP=83.192, HU-WBC=100.416, P<0.05), but no significant difference for U-IL-6 (HU-IL-6=2.585, P>0.05). The best Youden indexes of U-HBP and U-WBC diagnosing bacterial UTI were 0.475 and 0.441, respectively. The best cut-off level of U-HBP and U-WBC was 64.35 ng/ml and 119.25 cells/μl, respectively. Conclusions Testing the level of U-HBP was important for auxiliary diagnosing bacterial UTI, but testing U-IL-6 wasn't.

Research advances in the association between the adenosine triphosphate-binding cassette transporter A1 geneand coronary heart disease / 中华老年医学杂志

The human adenosine triphosphate-binding cassette transporter A1(ABCA1)gene is highly polymorphic.Some polymorphisms in promoters (rs2422493 ,rs2740483 ,etc. ) and exons (rs2230806 ,rs4149313 ,etc. )have been reported to be significantly associated with coronary heart disease(CHD ). In terms of the underlying mechanisms ,ABCA1 gene polymorphisms might be associated with CHD through modulating the levels of high-density lipoprotein cholesterol and other lipids ,or through changing ABCA1 protein structure and function. In this article ,the association of ABCA1 gene polymorphisms with CHD and the underlying mechanisms are reviewed.

The clinical value for plasma heparin-binding protein in the early diagnosis of the neonatal sepsis / 中华检验医学杂志

Objective To investigate the clinical value of plasmatic heparin-binding protein in early diagnosis and severity gradation of neonatal sepsis.Methods Thirty-nine patients with general sepsis,37 patients with severe sepsis and 16 patients with septic shock were recruited as corresponding study groups respectively,who all had been admitted to the Neonatal Intensive Care Units(NICU)of Hunan Children′s Hospital from December 2016 to August 2017,meanwhile,34 patients with local infection and 35 patients with non infection were enrolled as relevant control group respectively who all had been admitted to each neonatal ward in the retrospective study.The level of the heparin-binding protein(HBP), procalcitonin (PCT)and high sensitive C-reactive protein(hs-CRP)of all patients were detected respectively at the beginning of hospitalization.The difference of each group was compared by use of nonparametric statistics and the efficacy of every index on diagnosis of infection and sepsis was assessed with the receiver operating characteristic curve(ROC).Results The level of HBP in sepsis group,severe sepsis group and septic shock group HBP(H=91.764,P<0.01), PCT(H=51.757,P<0.01)and hs-CRP(H=28.418,P<0.01)are significantly higher than those in local infection group and non infection group;Plasmic HBP levels of severe sepsis group[52.35(33.65,88.15)(ng/ml)]and septic shock group[73.55(60.61,145.51)(ng/ml)]are statistically higher than general sepsis group[34.12(23.04,41.79)(ng/ml)](H=24.092, P<0.01).There are no statistically differences of serum PCT and hs-CRP among these three groups[(HPCT=1.909,Hhs-CRP=0.292),P>0.05].The area under the curve(AUC)of HBP in diagnosis of neonatal sepsis and infection are 0.885 and 0.904 respectively,more higher than PCT and hs-CRP;With the cut off value of 19.8 ng/ml,the sensitivity and specificity of HBP on diagnosis of infection are 85.7%and 82.9%respectively;the sensitivity and specificity 80.4% and 88.4% for neonatal sepsis with the cut-off value of 28.0 ng/ml respectively.Conclusion HBP probably has the better clinical value than PCT and hs-CRP in the early diagnosis and severity gradation of neonatal sepsis.

Screening and gene mutations analysis for neonates with methylmalonic aciduria / 中华围产医学杂志

Objective To investigate the characteristics of neonatal methylmalonic aciduria (MMA)regarding clinical manifestations,laboratory findings,gene mutations,treatments and prognosis.Methods Acylcamitine levels in blood samples of 207 308 neonates born from January 2016 to December 2017 in Xuzhou were detected by liquid chromatography tandem mass spectrometry and the abnormal results were further confirmed by detecting organic acids in urine samples with gas chromatography-mass spectrometry and gene sequencing analysis.Patients with isolated MMA were treated with dietary control and levocarnitine,while those complicated by homocysteinemia were treated with vitamin B12,levocarnitine,glycine betaine and calcium folinate.Clinical manifestations,laboratory findings,imaging features,genotypes,treatments and prognosis of patients with MMA were retrospectively analyzed.Paired sample t-test was applied for statistical analysis.Results MMA was eventually diagnosed in 12 patients,among which three were isolated MMA and nine were complicated by homocysteinemia.The three isolated MMA cases failed to response to vitamin B12 treatment without any symptoms on diagnosis.However,vitamin B12 was effective for the other nine patients,among which four had no clinical symptoms on diagnosis and five had manifestations such as slow response,recurrent vomiting,poor feeding,dyspnea,anemia and jaundice.Abnormal results of cranial MRI included bilateral basal ganglia damage,enlarged extracranial space,ventriculomegaly and changes in white matter.All patients underwent genetic analysis and three were found with MUT gene mutations and nine with MMACHC gene mutations.MUT gene mutations were classified into five types,including c.I106G＞A,c.1880A＞G,c.441T＞A,c.581C＞T and c.1741C＞T.Eight types of MMACHC gene mutations were identified,including c.609G＞A,c.658_660delAAG,c.482G＞A,c.1A＞G,c.567dupT,c.80A＞G,c.276+1G＞A and c.228_23 l delTGAC.Two mutations,c.276+lG＞A and c.228 23 ldelTGAC,were novel mutations.The most common mutation in MMACHC gene was c.609G＞A,followed by c.658_660delAAG and c.482G＞A.One of the isolated MMA patients died after refusing treatments and the other two showed significant decrease in serum propionylcarnitine,propionylcarnitine to acetylcarnitine ratio,serum homocysteine and methylmalonic acid and methylcitric acid in urine after treatment.Moreover,of the two patients who were alive at follow-up,one experienced normal growth and development and the other suffered from growth retardation.The ratio of propionylcamitine to acetylcarnitine and the levels of serum propionylcarnitine,serum homocysteine and methylmalonic acid and methylcitric acid in urine were significantly decreased in the nine patients with MMA complicated by homocystinuria after one month of treatment [0.88±0.35 vs 0.13±0.05,(7.12±1.90) μ mol/L vs (3.18±1.08) μ mol/L,(136.48±38.14) μ mol/L vs (34.41±17.33) μmol/L,103.51±69.62vs 5.35±2.15 and 7.95±6.88 vs 1.02±0.48,t=-6.166,-6.687,-12.941,-4.208 and-3.015,respectively,all P＜0.05].Two deaths,three asymptomatic and four psychomotor retardation patients were reported during follow-up.Conclusions Newborn screening with liquid chromatography tandem mass spectrometry is important for early diagnosis of MMA.MMACHC gene defects are the main causes of MMA in Xuzhou area and the predominant one is c.609G＞A mutation.Prognosis of MMA might be related to disease type,age of onset and patient's reactivity to vitamin B12.

Diagnostic value of plasma heparin-binding protein and pentraxin 3 in neonatal bacterial infection diseases / 中华检验医学杂志

Objective To evaluate the diagnosis value of heparin-binding protein ( HBP ) and pentraxin 3 ( PTX3 ) in neonatal bacterial infectious diseases . Methods A retrospective study was conducted on 30 septic neonatal as neonatal sepsis group and 84 local infection neonatal as general infection group from May to November 2017 in Renmin Hospital of Wuhan University .It also selected 50 high bilirubin hematic disease but without infection or shock neonatal ( control group ) .A total of 114 neonatal bacterial infection ( neonatal sepsis group and general infection group ) were divided into shock group ( 39 cases) and non-shock group ( 75 cases ) . The levels of plasma HBP and PTX3 were tested with immunoturbidimetry and ELSIA respectively .The results of procalcitonin ( PCT ) and white blood cells (WBC) counts were collected.Non-parametric test were performed for non-normal distribution data; the diagnostic performances of data were evaluated by receiver operating characteristic ( ROC) curve; pearson correlation coefficient was performed for correlation analysis .Results Plasma levels of HBP in neonatal sepsis group, general infection group and control group were (64.41 ±78.51) ng/ml, (47.16 ±50.59) ng/ml and (31.97 ±20.76) ng/ml, respectively; plasma levels of PTX3 were (2.23 ±1.44) ng/ml, (1.76 ±0.94) ng/ml and (1.26 ±0.66) ng/ml, respectively;serum levels of PCT were (31.92 ±36.65) ng/ml,( 7.72 ±9.28 ) ng/ml and ( 1.87 ±5.02 ) ng/ml, respectively.The levels of PTX3 and PCT in neonatal sepsis group were significantly higher than in general infection group (Z=3.74, Z=5.01, all P<0.05) and control group (Z=3.98, Z=5.20, all P<0.05).The levels of HBP in neonatal sepsis group were significantly higher than in control group ( Z =2.37, P <0.05 ), but there were no significant difference in neonatal sepsis group and general infection group (Z=1.16, P>0.05).The levels of PTX3 and PCT in shock group were significantly higher than in non-shock group ( Z=2.20, Z=3.70, all P<0.05), but there were no significant difference in plasma HBP of shock and non-shock group ( Z=0.37, P>0.05).The area under curve (AUC) of HBP, PTX3 and PCT were 0.683, 0.802 and 0.869 respectively in the diagnosis of neonatal bacterial infection diseases .The biggest AUC of combined diagnosis of HBP, PTX3 and PCT was 0.910.There was a positive correlation between PTX 3 and PCT ( r=0.242, P<0.05) .Conclusions PTX3 and PCT could probably be acted as an important biomarker for diagnosis of neonatal bacterial infection diseases , and combined diagnosis of HBP , PTX3 and PCT could be superior to single biomarker diagnosis.

The role of heparin-binding protein, procalcitonin, C-reactive protein and white blood cell in respiratory tract bacterial infection / 中华检验医学杂志

Objective To evaluate the diagnostic value of the heparin-binding protein (HBP),procalcitonin (PCT),C-reactive protein (CRP),white blood cell (WBC) in respiratory tract bacterial infection.Methods 66 respiratory tract bacterial infection patients,37 respiratory tract non-bacterial infection patients and 39 control group in the Third Xiangya Hospital from October 2015 to March 2017 was selected as objects in this prospective study.The levels of HBP,PCT and CRP in blood of the objects were tested with ELESA,immunofluorescence assay,immunoturbidimetry respectively;WBC counts were taken by Sysmex XE-5000 blood analyzer.The difference among the three groups was analyzed by Student's t test,one-way ANOVA or Wilcoxon test.Receiver operating characteristic curve was utilized to analyze the diagnostic value of HBP,PCT,CRP and WBC in respiratory tract bacterial infection.Results The plasma level of HBP were 36.30 (7.78-89.36) ng/ml,5.57 (4.37-8.23) ng/ml,2.84 (1.53-6.51) ng/ml in respiratory tract bacterial infection group,respiratory tract non-bacterial infection group and control group respectively.The socre of PCT were 0.08 (0.04-0.83) ng/ml,0.09 (0.04-0.30) ng/ml,0.04 (0.03-0.08) ng/ml.The socre of CRP were 56.20 (19.33-76.23) mg/L,34.40 (2.15-83.95) mg/L,(2.20 ± 0.99) mg/L.The socre of WBC count were (10.59 ±4.58) × 109/L,8.40 (5.80-11.88) × 109/L,(6.14± 1.31) × 109/L.There were statistically significant differences in HBP scores between respiratory tract bacterial infection group and respiratory tract non-bacterial infection group or control group (Z =-4.828,P ＜0.001;Z =-5.685,P ＜ 0.001).There were no statistically significant differences in PCT,CRP and WBC scores between respiratory tract bacterial infection group and non-bacterial infection group (F =0.045,P ＞ 0.05;F =0.100,P ＞ 0.05;F =2.417,P ＞ 0.05),but significant differences between respiratory tract bacterial infection group and control group (Z =-2.881,P ＜ 0.05;Z =-6.595,P ＜ 0.001;t =6.499,P ＜ 0.001).The area under curve (AUC) of HBP,PCT,CRP and WBC diagnosing respiratory tract bacterial infection was 0.89,0.69,0.95 and 0.85 respectively.The AUC of HBP differential diagnosising was 0.80.Conclusion HBP can be used as an efficient supplementary indicator for respiratory tract bacterial infection,the differential diagnostic value is superior to PCT,CRP and WBC.

Differentiation of Multiple System Atrophy and Parkinson's Disease Using 11C-CFT PET/CT / 中国医学影像学杂志

Purpose To investigate the value of 11C-CFT PET/CT dopamine transporter (DAT) imaging in differential diagnosis of multiple system atrophy (MSA) and Parkinson's disease (PD).Materials and Methods The 11C-CFT PET/CT images of clinically confirmed MSA patients (21 cases),PD patients (24 cases) and healthy adults (10 cases as normal control) were analyzed retrospectively.The volume of interest (VOI) were drawn manually,and the DAT binding indexes and asymmetry indexes of different regions of striatum,including caudate and putamen,were calculated.The differences of DAT binding indexes and asymmetry indexes among the above three groups were analyzed.Results Compared with the normal control group,the striatal DAT binding indexes of MSA group or PD group were significantly reduced (P＜0.05).There were no significant differences in DAT binding indexes between the MSA group and the PD group (P＞0.05).Compared with the normal control group,the DAT binding asymmetry indexes were significantly increased in the PD group (P＜0.05),but the indexes showed no significant differences in MSA group (P＞0.05).The DAT asymmetry indexes of caudate and putamen in the PD group were higher than those in the MSA group (P＜0.05).Conclusion 11C-CFT PET/CT imaging can detect the degeneration of dopaminergic neurons in striatum.The number of striatal dopamine transporters declines in both MSA and PD patients,but the asymmetry of striatal dapamine transporter in PD patients is higher than that in MSA patients.11C-CFT PET/CT can differentiate MSA and PD.

Comparative research of inflammatory factors in child patients with sepsis / 中华检验医学杂志

Objective To investigate clinical value of inflame factors in child patients with sepsis at different time points before the diagnosis time.Methods A retrospective model was performed in this study.24 child patients with sepsis in Department of Paediatrics from January 2014 to October 2016 were selected.At the time 72 h(group A),48 h(group B),24 h(group C) before the diagnosis time,plasma levels of HBP and serum levels of IL-6,IL-10 were detected by ELISA,and pre calcitonin (PCT) and high sensitive C reactive protein (hs-CRP) were detected by immunofluorescence.Compared to the same period,22 healthy cases were selected as the control.Repeated measure anova and Receiver operating characteristic curve analysis were performed.Results The plasma levels of HBP were (9.69 ± 1.30) μg/L,(12.82 ±2.03) μg/L,(15.46 ± 1.02) μg/L,(18.60 ± 1.10) μg/L at group A,group B,group C before the diagnosis time respectively.The plasma levels of HBP at all time points before the diagnosis time were significantly higher than the control (t =6.27,P ＜ 0.01;t =16.82,P ＜ 0.01;t =25.16,P ＜ 0.01).The serum levels of HBP at group B,group C were significantly higher than the last time point (t =5.62,P ＜0.01;t =10.25,P ＜ 0.01).Receiver operating characteristic curve(ROC) revealed that the areas of HBP at group A(0.823),group B (0.898),was significantly higher than the other inflame factors(Z =2.41,P ＜0.01;Z=2.02,P＜0.05;Z=0.38,P＞0.05;Z=0.32,P＞0.05)(Z=0.43,P＞0.05;Z=0.46,P＞0.05;Z =0.26,P ＞ 0.05;Z =0.57,P ＞ 0.05).It also revealed that at group C,area of PCT(0.941) was significantly higher than the other inflame factors (Z =0.12,P ＞ 0.05;Z =0.08,P ＞ 0.05;Z =0.03,P ＞0.05;Z-0.10,P ＞ 0.05).Conclusions HBP has a wide diagnostic window period for sepsis.IL-6,IL-10,PCT and hs-CRP have diagnostic value in partial periods of sepsis.

Comparison of the clinical value of plasma heparin-binding protein, procalcitonin and C-reactive protein in the early diagnosis of sepsis / 中华检验医学杂志

Objective To assess the clinical utility of measurement of plasma heparin-binding protein (HBP) in diagnosis and prognosis of sepsis.Methods This is a retrospective study on the performance of plasma heparin-binding protein, procalcitonin and C-reaction protein in the early diagnosis of sepsis. Thirty-one patients with sepsis, 16 patients with severe sepsis, 12 patients with septic shock and 37 control patients without confirmed sepsis, all admitted to the Intensive Care Units (ICU) of the Third Hospital Affiliated to Wenzhou Medical University and Wenzhou Central Hospital from August 2014 to November 2016, were enrolled in the study. The plasma level of HBP, procalcitonin (PCT) and C-reactive protein (CRP) were measured, and the detailed clinical data were retrieved from the patient chart records for all patients described above. Comparison of each laboratory and clinical parameters between groups was carried out by Non-parameter Test. The efficiency of each parameter was calculated by receiver operating characteristics curves (ROC) analysis. The correlation between HBP, PCT or CRP and clinical or other laboratory parameters was explored using Spearman correlation analysis.Results HBP was significantly elevated in patients with severe sepsis[(100.65±58.82)ng/ml and(31.86±36.87)ng/ml,Z=-3.856,P<0.05;(100.65±58.82)ng/ml and(24.96±17.49)ng/ml,Z=-3.556,P<0.05]and in patients with septic shock[(148.28±99.73)ng/ml and(31.86±36.87)ng/ml,Z=-4.432,P<0.05;(148.28±99.73)ng/ml and(24.96±17.49)ng/ml,Z=-4.157,P<0.05], respectively, while CRP[(154.64±62.90)mg/L and(92.56±67.49)mg/L,Z=-2.749,P<0.05;(154.64±62.90)mg/L and (79.21±51.80)mg/L,Z=-3.218,P<0.05]and PCT[(32.86±39.93)ng/ml and(2.70±6.24)ng/ml,Z=-3.395,P<0.05;(32.86±39.93)ng/ml and(4.21±14.94)ng/ml,Z=-4.092,P<0.05]were increased only in patients with septic shock (P<0.05).For HBP, the area of under the ROC curves (AUC) was the biggest (AUC=0.687), indicating the clinical significance(P<0.05) with excellent sensitivity(0.729) at the optimal cut-off value(18.58 ng/ml). In addition, HBP(APTT: r=0.244, P=0.016;PT: r=0.351, P<0.001;INR: r=0.314, P=0.002;D-Dimer: r=0.334, P=0.001;lactic acid: r=0.394, P<0.001), CRP(APTT: r=0.271, P=0.008;PT: r=0.348, P=0.001;INR: r=0.264, P=0.009;D-Dimer: r=0.257, P=0.012;lactic acid: r=0.329, P=0.001) and PCT(APTT: r=0.375, P<0.001;PT: r=0.523, P<0.001;INR: r=0.535, P<0.001;D-Dimer: r=0.254, P=0.013;lactic acid: r=0.422, P<0.001)were positively correlated to coagulation function and to lactate.Conclusion HBP could probably be acted as an important biomarker for diagnosis and prognosis for patients with sepsis, esp., for patients with severe sepsis and septic shock.

MMACHC gene mutation analysis in the prenatal diagnosis of methylmalonic aciduria with homocystinuria / 中华检验医学杂志

Objective To analyse MMACHC mutations for 45 pedigrees with combined methylmalonic aciduria and homocyctinuria by Sanger sequencing, and to discuss the utility of prenatal genetic diagnosis for these pedigrees.Method Peripheral blood was collected from 45 probands and their parents from 2012-2015 in Genetic Counselling Clinic of the First Affiliated Hospital of Zhengzhou University, and the DNA were extracted from the blood.Then the coding sequence of MMACHC gene was amplified by PCR, and the PCR products were further sequenced to detect mutations for each pedigree.For 12 families, chorionic villus sampling was performed on the pregnant women to make prenatal genetic diagnosis.Result There were 14 distinct mutations detected in the 45 pedigrees, and the most frequent mutations are c.609G>A(W203X),c.658-660delAAG(K220del)and c.80A>G (Q27A).Two of those mutations have not been reported before:one is a splicing site mutation c.81+1G>A;while the other is a missense mutation c.665A>G,p.Y222C.Most mutations were found in exon 4.Among the 12 pedigrees who received prenatal diagnosis, 2 fetuses were normal, 7 fetuses were carriers of heterozygous mutation, and the other 3 fetuses were patients with compound heterozygous mutation or homozygous mutation.The couples whose fetuses were normal or carriers continued the gestation, while the couples whose fetuses were patients decided to terminate the pregnancy.After delivery, the outcome of the fetuses was the same as the prenatal diagnose results.Conclusion Two novel mutations of MMACHC were identified and prenatal genetic diagnosis helps to avoid the delivery of combined methylmalonic aciduria and homocyctinuria patients.

Combined measurement of H-FABP and MPO in the prognosis of non-ST elevation acute cornary syndromes / 国际检验医学杂志

Objective To evaluate the prognosis value of heart‐type fatty‐acid binding protein(H‐FABP)and myeloperoxidase (MPO) in non‐ST elevation acute coronary syndromes(NSTE ACS) .Methods 181 NSTE ACS patients were divided into 4 groups according to the level of H‐FABP and MPO ,and the baselines of 4 groups such as gender ,age ,hypertension ,smoking ,body mass in‐dex ,diabetes mellitus ,hyperlipidemia were compared .The incidences of adverse cardiac events in 4 groups were compared after a 2 years′follow‐up .Results By multivariate COX regression adjustment for other risk factors ,the relative risk(RR) of H‐FABP for adverse cardiac events was 2 .023(95% CI:1 .029 -3 .987 ,P=0 .002) ,and MPO was (95% CI:2 .196 -5 .325 ,P< 0 .05) .The 2 years′follow‐up showed the incidence of adverse cardiac events in NSTE ACS patients with higher H‐FABP and MPO levels was higher than the NSTE ACS patients with one or two indicators of normal levels .Conclusion The combined application of H‐FABP and MPO could has clinical significance for the prognosis of patients with NSTE ACS .

Expression of APPL1 in gastric carcinomas and its clinical significance / 中国医师杂志

Objective To investigate the expression and significance of adaptor protein containing PH domain,PTB domain,and leucine zipper motif 1 (APPL1) in gastric cancers.Methods Expressions of APPL1 protein and mRNA were detected with immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 47 surgical specimens of gastric carcinomas (GC) and 27 normal gastric tissue specimens,respectively.Results The expression rate of APPL1 protein was 59.6％ (28/47) in GCs,and 26.1％ (6/23) in normal gastric tissues,with a statistically significant difference between two groups (P ＜0.05).The relative expression of mRNA was 0.821 ±0.141 in GCs,and 0.731 ±0.112 in normal gastric tissues,with a statistically significant difference between two groups (P ＜ 0.05).Conclusions The expressions of APPL1 protein and mRNA are increased in GCs,with a close relationship between GC and APPL1.

Aβ25-35 induce endoplasmic reticulum stress and apoptosis of rat cardiomyocytes / 中国医师杂志

Objective To investigate the effects of amyloid-β (Aβ)25-35 on endoplasmic reticulum (ER) stress and apoptosis in cultured rat cardiomocytes,and to elucidate the role of ER stress in the injury of cardiomocytes induced by Aβ25-35.Methods The isolated rat myocardial cells were cultured in vitro.Following stimulation of Aβ25-35 with different dose,the survival ratio was observed with methyl thiazolyl tetrazolium (MTT) method.Hoechst33258 staining was used to observe the morphology of apoptotic changes.The percentage of apoptotic cardiomyocytes was quantified with flow cytometry.The expressions of ER stree proteins,including X box-binding protein-1 (XBP-1),glucose-regulated protein 78 (GRP78),and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured with Western blot.The cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) were measured with Western blot.Results Aβ25-35 decreased the survival ratio and induced the apoptosis of cultured rat cardiomocytes in dose-dependent mode.Meanwhile,Aβ25-35 increased the expressions of ER stree proteins,including XBP-1,GRP78,and CHOP.Aβ25-35 increased the expressions of cleaved caspase-3 and cleaved PARP.Conclusions Aβ25-35 could induce the apoptosis of rat cardiomyocytes,which were involved in ER stress possibly.This study might provide a new strategy for clinical treatment of Alzheimer's disease (AD)-associated myocardial injury.

T300A GENETIC POLYMORPHISM: a susceptibility factor for Crohn?s disease? / Polimorfismo genético T300A: fator de susceptibilidade para doença de Crohn?

Context Crohn’s disease is characterized by a chronic and debilitating inflammatory disorder of the gastrointestinal tract. Several factors may contribute to its development. From extensive studies of the human genome, the polymorphism T300A of the gene ATG16L1 (autophagy-related 16-like 1) has been related to increased risk of developing this disease. Objectives Analyze the role of polymorphism T300A (rs2241880) in patients with Crohn’s disease. Methods 238 samples from (control group) and 106 samples from patients with Crohn’s disease recruited at five Southern Brazilian reference centers were evaluated. The genotyping consisted of the amplification via Polymerase Chain Reaction of the genomic segment encompassing T300A, followed by Restriction Fragment Length Polymorphism analysis. The amplicons and fragments were separated by agarose gel electrophoresis and confirmed under ultraviolet light. Results The genotype AG was more prevalent among patients and controls (50% vs 44.8%), followed by genotypes AA (26.4% vs 35.1%) and GG (23.6% vs 20.1%). The frequency of the allele G of the polymorphism T300A was higher in the group of patients with Crohn’s disease (48.6%) than in controls (42.4%), although not reaching statistical significance. Conclusions It was not possible to confirm the increased susceptibility on development of Crohn’s disease conferred by polymorphism T300A. .

Contexto A doença de Crohn caracteriza-se por uma desordem inflamatória, crônica e debilitante do trato gastrointestinal. Diversos fatores contribuem para seu desenvolvimento. A partir da realização de estudos amplos do genoma, o polimorfismo T300A do gene ATG16L1 (autophagy-related 16-like 1) tem sido relacionado com aumento de susceptibilidade ao desenvolvimento desta doença. Objetivos Analisar a incidência do polimorfismo T300A (rs2241880) em pacientes com doença de Crohn. Métodos Foram analisadas 238 amostras de doadores de sangue (grupo controle) e 106 amostras de pacientes com doença de Crohn, procedentes de cinco centros. A genotipagem consistiu em amplificação do segmento gênico T300A, via reação em cadeia da polimerase, seguidos da análise de polimorfismo de comprimentos dos fragmentos de restrição. Os amplicons e fragmentos foram separados via eletroforese em gel de agarose e visualizados sob luz ultravioleta. Resultados O genótipo AG foi mais prevalente entre os pacientes e controles (50% vs 44,8%), seguido dos genótipos AA (26,4% vs 35,1%) e GG (23,6% vs 20,1%). A freqüência do alelo G do polimorfismo T300A foi maior no grupo de pacientes com doença de Crohn (48,6%) do que nos controles (42,4%), embora sem significância estatística. Conclusões Não foi possível confirmar o aumento de susceptibilidade à doença de Crohn conferido pelo polimorfismo T300A. .

Construction and identification of pIRES2-GDNF-VEGF165 bicistronic eukaryotic expression vector / 中国组织工程研究

BACKGROUND:Human glial cellline-derived neurotrophic factor (GDNF) and vascular endothelial growth factor 165 (VEGF 165 ) are essential genes for celldifferentiation. OBJECTIVE:To construct and identify pIRES 2-GDNF-VEGF 165 bicistronic eukaryotic expression vector. METHODS:Human GDNF genes were obtained from the genomic DNA of human peripheral blood mononuclear cells by PCR. Then the GDNF cDNA fragment was inserted into the multiple cloning sites of pIRES 2-EGFP, to generate the bicistronic eukaryotic expression plasmid pIRES 2-GDNF-EGFP. The VEGF 165 gene was obtained from pIRES 2-VEGF 165-EGFP plasmid by twin PCR. Then VEGF 165 cDNA fragment was cloned into the pIRES 2-GDNF-EGFP, instead of EGFP, to create a double gene co-expressing vector plasmid pIRES 2-GDNF-VEGF 165 containing internal ribosome entry sites. Then pIRES 2-GDNF-VEGF 165 was used to transfect HEK293 cells. RT-PCR and western blot analysis were performed to test the co-expression of double genes. RESULTS AND CONCLUSION:DNA sequencing analysis demonstrated that the GDNF and VEGF 165 were exactly consistent with the sequence recorded in the GenBank. The size of GDNF gene was 636 bp and the size of VEGF165 gene was 576 bp. Enzyme digestion analysis indicated that, pIRES2-GDNF-VEGF165 bicistronic eukaryotic expression vector inserted GDNF band by Bgl II/Bam HI, inserted IRES-VEGF 165 fragment by Bam HI/Not I, and inserted GDNF-IRES-VEGF165 fragment by Bgl II/Not I. RT-PCR and western blot analysis showed that, after HEK293 cells were transfected with pIRES 2-GDNF-VEGF 165 , double genes were expressed at the mRNA and protein levels. The pIRES 2-GDNF-VEGF 165 bicistronic eukaryotic expression vector is successful y constructed.

Diagnostic value of serum NGAL and Cys-C for early renal damage in aged patients with chronic heart ;failure of coronary heart disease / 心血管康复医学杂志

Objective:To explore the relationship among serum neutrophil gelatinase associated lipocalin (NGAL), cystatin C (Cys-C) levels and cardiac, renal function;and diagnostic value of NGAL and Cys-C for early renal damage in aged patients With coronary heart disease (CHD).Methods:According to NYHA cardiac function classi-fication,a total of 84 aged CHD patients Were divided into class I group (n=30),class Ⅱ group (n=28)and classⅢ-Ⅳ group (n=26).Another 31 aged healthy objects Were selected as healthy control group.Serum N terminal pro B-type natriuretic peptide (NT-proBNP),NGAL and Cys-C etc. levels Were measured,and the correlation a-mong serum NGAL,Cys-C levels and cardiac function,estimated glomerular filtration rate (eGFR)Were analyzed. The accuracy of serum NGAL and Cys-C diagnosing renal insufficiency Was evaluated by receiver operator character-istic curve (ROC).Results:Along With NYHA class increased,there Were significant increase in serum levels of NGAL [(36.96±21.23)μg/L vs.(87.80±61.40)μg/L vs.(141.21±92.96)μg/L vs.(198.15±98.46)μg/L] and Cys-C [(0.75±0.64)mg/L vs.(1.40±1.88)mg/L vs.(2.33±2.03)mg/L vs.(3.45±1.81)mg/L]in healthy control group,NYHA I,Ⅱ,Ⅲ-Ⅳ groups,and they Were highest in NYHA class Ⅲ-Ⅳ group,there Was significant difference in serum NGAL level betWeen any tWo groups among the four groups (P0.05). Pearson correlation analysis indicated that serum NGAL and Cys-C levels Were positively correlated With NT-proBNP (r=0.842,0.718,P<0.01 both),and negatively correlated With eGFR (r=-0.689,-0.448,P<0.01 both), and serum NGAL level had closer correlation With NT-proBNP and eGFR.Area under ROC of serum NGAL and Cys-C Were 0.884 and 0.744 respectively in diagnosing renal insufficiency.Conclusion:Serum NGAL and Cys-C lev-els have good correlation With cardiac and renal function in aged CHD patients,Which are sensitive and accurate in-dexes for diagnosing early renal damage.