Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis

OBJECTIVE To evalu ate the role of resting magnetocardiography in identifying seve re coronary artery stenosis in patients with suspected coronary artery disease.METHODS A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography:the non-severe coronary stenusis group(<70% stenosis) and the severe coronary stenosis group(≥70% stenosis).The diagnostic model was constructed using magnetic field map(MFM) parameters,either individually or in combination with clinical indicators.The performance of the models was evaluated using receiver operating characteristic curves,accuracy,sensitivity,specificity,positive predictive value(PPV) and ne gative predictive value(NPV).Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models,respectively.RESULTS In the severe coronary stenosis group,QR_MCTDd,S_MDp,and TT_(MA)C_(50) were significantly higher than those in the non-severe coronary stenosis group(10,46±10.66 vs,5.11±6.07,P <0.001;7.2±8.64 vs.4.68±6.95,P=0.003;0.32±57.29 vs.0.26±57.29,P <0.001).While,QR_MV_(amp),R_(MA),and T_(MA) in the severe coronary stenosis group were lower(0.23±0.16 vs.0.28±0.16,P<0.001;55.06±48.68 vs.59.24±53.01,P<0.001;51.67±39.32 vs. 60.45±51.33,P <0.001).Seven MFM parameters were integrated into the model,resulting in an area under the curve of 0.810(95% CI:0.765-0.855).The sensitivity,specificity,PPV,NPV,and accurecy were 71.7%,80.4%,93.3%,42.8 %,and 73.5%;respectevely.The combined model exhibited an area under the curve of 0.845(95% CI:0.798-0.892).The sensitivity,specificity,PPV,NPV,and accuracy were 84.3%,73.8%,92.6%,54.6%,and 82.1%;respectively.Calibration curves demonstrate d excellent agreement between the nomogram prediction and actual observation.The decision curve analysis showed that the c ombine d model provided greater net benefit compared to the magnetocardingraphy model.CONCLUSIONS The novel quantitative MFM parameters,whether used individually or in combination with clinical indicators,have been shown to effectively pre dict the risk of severe coronary stenosis in patients presenting with angina-like symptoms.Magnetocardiography,an emerging non-invasive diagnostic tool,warrants further exploration for its potential in diagnosing coronary heart disease.

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.

A synthetic optically pumped gradiometer for magnetocardiography measurements

Magnetocardiography(MCG)measurement is important for investigating the cardiac biological activities.Traditionally,the extremely weak MCG signal was detected by using superconducting quantum interference devices(SQUIDs).As a room-temperature magnetic-field sensor,optically pumped magnetometer(OPM)has shown to have comparable sensitivity to that of SQUIDs,which is very suitable for biomagnetic measurements.In this paper,a synthetic gradiometer was constructed by using two OPMs under spin-exchange relaxation-free(SERF)conditions within a moderate magnetically shielded room(MSR).The magnetic noise of the OPM was measured to less than 70 fT/Hz1/2.Under a baseline of 100 mm,noise cancellation of about 30 dB was achieved.MCG was successfully measured with a signal to noise ratio(SNR)of about 37 dB.The synthetic gradiometer technique was very effective to suppress the residual environmental fields,demonstrating the OPM gradiometer technique for highly cost-effective biomagnetic measurements.

Screening and identification of interacting proteins with hepatitis B virus core protein in leukocytes and cloning of new gene C1

AIM： To investigate the biological function of HBcAg in pathogenesis of HBV replication in peripheral blood mononuclear cells （PBMCs）.METHODS： HBcAg region was amplified by polymerase chain reaction （PCR） and HBV HBcAg bait plasmid pGBKT7-HBcAg was constructed by routine molecular biological methods. Then the recombinant plasmid DNA was transformed into yeast AH109. After the HBV core protein was expressed in AH109 yeast strains （Western blot analysis）, yeast-two hybrid screening was performed by mating AH109 with Y187 containing leukocyte cDNA library plasmid. Diploid yeast cells were plated on synthetic dropout nutrient medium （SD/-Trp-Leu-His- Ade） （QDO） and synthetic dropout nutrient medium （SD/-Trp-Leu-His-Ade） （TDO）. The second screening was performed with the LacZ report gene （ yeast cells were grown in QDO medium containing X-a-gal）. The interaction between HBV core protein and the protein obtained from positive colonies was further confirmed by repeating yeast-two hybrid. After plasmid DNA was extracted from blue colonies and sequenced, the results were analyzed by bioinformatic methods.RESULTS： Eighteen colonies were obtained and sequenced, including hypermethylated in cancer 2 （3 colones）, eukaryotic translation elongation factor 2 （2 colones）, acetyl-coenzyme A synthetase 3 （1 colone）, DNA polymerase gamma （1 colone）, putative translation initiation factor （1 colone）, chemokine （C-C motif） receptor 5 （1 colone）, mitochondrial ribosomal protein L41 （1 colone）, kyot binding protein genes （1 colone）, RanBPM （1 colone）, HBeAg-binding protein 3 （1 colone）, programmed cell death 2 （1 colone）. Four new genes with unknown function were identified.CONCLUSION： Successful cloning of genes of HBV core protein interacting proteins in leukocytes may provide some new clues for studying the biological functions of HBV core protein.

Screening of genes of proteins interacting with p7 protein of hepatitis C virus from human liver cDNA library by yeast two-hybrid system

AIM： To investigate the biological function of p7 protein and to look for proteins interacting with p7 protein in hepatocytes. METHODS： We constructed p7 protein bait plasmid by cloning the gene of p7 protein into pGBKTT, then transformed it into yeast AH109 （a type）. The transformed yeast was mated with yeast Y187 （α type） containing liver cDNA library plasmid, pACT2 in 2×YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium （SD/- Trp-Leu-His-Ade） containing x-α-gal for selection and screening. After extracting and sequencing of plasmids from blue colonies, we performed sequence analysis by bioinformatics. RESULTS： Fifty colonies were selected and sequenced. Among them, one colony was Homo sapiens signal sequence receptor, seven colonies were Homo sapiens H19, seven colonies were immunoglobulin superfamily containing leucine-rich repeat, three colonies were spermatid peri-nuclear RNA binding proteins, two colonies were membrane-spanning 4-domains, 24 colonies were cancer-associated antigens, four colonies were nudeoporin 214 ku and two colonies were CLL-associated antigens. CONCLUSION： The successful cloning of gene of protein interacting with p7 protein paves a way for the study of the physiological function of p7 protein and its assodated protein.

Screening of hepatocyte proteins binding to F protein of hepatitis C virus by yeast two-hybrid system

AIM： To investigate the biological function of F protein by yeast two-hybrid system. METHODS： We constructed F protein bait plasmid by cloning the gene of F protein into pGBKT7, then recombinant plasmid DNA was transformed into yeast AH109 （a type）. The transformed yeast AH109 was mated with yeast Y187 （α type） containing liver cDNA library plasmid in 2×YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium （SD/-Trp-Leu-HisAde） containing X-α-gal for selection and screening. After extracting and sequencing plasmids from positive （blue） colonies, we underwent sequence analysis by bioinformatics. RESULTS： Thirty-six colonies were selected and sequenced. Among them, 11 colonies were zymogen granule protein, 5 colonies were zinc finger protein, 4 colonies were zinc-α-2-glycoprotein, 1 colony was sialyltransferase, 1 colony was complement control protein factor I, 1 colony was vitronectin, and 2 colonies were new genes with unknown function. CONCLUSION： The yeast two-hybrid system is an effective method for identifying hepatocyte proteins interacting with F protein of hepatitis C virus. F protein may bind to different proteins. 2005 The WJG Press and Elsevier Inc. All rights reserved

Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness

Frequent traffic accidents constitute a major danger to human beings.The accident-prone driver who has the stable physiological,psychological,and behavioral characteristics is one of the most prominent causes of traffic accidents.The internal link between the individual characteristics and the accident proneness has been a difficult point in the accident prevention research.The authors selected accident-prone drivers as cases and safe drivers as controls(case-control group) from 18,360 drivers who were enrolled from three public transportation incorporations of China using area stratified sampling method.The case-control groups were 1:1 matched.The authors performed genome-wide association study(GWAS) by 179 cases and 179 controls using the U.S.Affymetrix Genome-Wide Human Mapping SNP 6.0Array.The authors observed that the gene frequencies of34 single-nucleotide polymorphisms(SNPs) in three regions of cases were higher than those in the control(P < 10^(–4)).The authors then tested two independent replication sets for strong association 6 SNPs in 349 pairs of case-control drivers using the U.S.ABI 3730 sequencing method.The results indicated that SNP rs6069499 within linked CBLN4 gene are strongly associated with accident proneness(Pcombined= 6.37×10^(-10)).According to CBLN4 gene mainly involved in adrenal development and the regulation of secretion,the authors performed 12 biochemical parameters of the blood using radioimmunoassay.The levels of dopamine(DA) and adrenocorticotropic(ACTH)hormone showed significant differences between accidentprone drivers and safe drivers(P_(DA)= 0.03,P_(ACTH)= 0.01).It is suggested that the accident-prone drivers may have the idiosyncrasy of susceptibility.

A Specification Test of Stochastic Diffusion Models

In this paper, we propose a hypothesis testing approach to checking model mis-specification in continuous-time stochastic diffusion model. The key idea behind the development of our test statistic is rooted in the generalized information equality in the context of martingale estimating equations. We propose a bootstrap resampling method to implement numerically the proposed diagnostic procedure. Through intensive simulation studies, we show that our approach is well performed in the aspects of type I error control, power improvement as well as computational efficiency.

Strengthening Project Management to Attain Overseas Blocks with High Potential for Exploration

New overseas venture evaluation is key for oversea exploration of Chinese oil companies,whose credibility directly determine the degree of success of exploration for overseas blocks.The uniqueness of new overseas venture evaluation in short assessing cycle and limited data make project management vital.Project management includes human resource allocation,quality control and effective communication.In China National Offshore Oilfield Corporation(CNOOC),the new overseas venture evaluation system has been established.This system includes quality control system and assurance for new overseas venture evaluation,geological evaluation norms for overseas oil & gas exploration,regulations for new overseas venture evaluation and seismic interpretation methodology and procedure for new overseas venture evaluation.Directed by the new overseas venture evaluation system,three-level quality control and management of data-room visit are strictly reinforced,which guarantees the efficiency and quality of new overseas venture evaluation.As a result the new overseas venture evaluation boosts the development of young explorationists and leads to breakthroughs in exploring potential target areas of CNOOC and in the discovery of giant oil and gas fields,which underpins the development of overseas business in CNOOC.