Overview and outlook of CT quantification technology for chronic obstructive pulmonary disease / 西安交通大学学报(医学版)

Chronic obstructive pulmonary disease (COPD) is a type of disease with diverse clinical manifestations and strong heterogeneity; thus early diagnosis is difficult. Patients at stable period often suffer from poor life quality. Frequent hospitalization induced by acute exacerbations has high social and economic burdens. COPD is predicted to be the third leading cause of death in the world by 2020 and the fifth leading cause of disability. At present, there is a lack of accurate quantitative technology. Our research team, in bearing of the Public Welfare Special Industry of National Health Commission "Diagnostic and Evaluation System of Respiratory Diseases Based on Digital Lung" and on the basis of CT quantitative technology, investigated the morphological changes of pulmonary parenchyma, bronchi and pulmonary vessels as well as their correlations. We provide an individualized, standardized and comprehensive evaluation for COPD patients. In this paper we also discuss the hot issues of COPD and point out the future research direction.

SKOV-3 cell imaging by paramagnetic particles labeled with hairpin cell-penetrating peptides / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The hairpin cell-penetrating peptides (hCPPs) demonstrate an interesting characteristic of conditioned activation by molecules. We hypothesized that hCPPs have the potential to selectively deliver a paramagnetic gadolinium probe into the matrix metalloproteinase 2 (MMP-2) positive human ovary adenocarcinoma cell lines, SKOV-3.</p><p><b>METHODS</b>hCPPs were synthesized and labeled with 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid gadolinium (III) (Gd-DOTA) and fluorescein isothiocyanate (FITC) by f-moc strategy using a standard solid phase peptide synthesis protocol. MMP-2 expression and activity were demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) and zymography. Internalization and location of hCPPs in SKOV-3 cells were observed by fluorescein imaging and flow cytometery. Selective delivery of Gd-DOTA in SKOV-3 cells was observed by magnetic resonance imaging (MRI) and transmission electron microscopy (TEM).</p><p><b>RESULTS</b>The uptake of hCPPs by SKOV-3 cells depended on the activity of MMP-2. T1WI signals of SKOV-3 cells treated with Gd-DOTA-hCPPs suggested the uptake of Gd-DOTA-hCPPs increased in a time- (r = 0.990, P < 0.01) and concentration-dependent manner (r = 0.964, P < 0.001), but was inhibited by a MMP-2 inhibitor. Electron-dense particles observed in the cytoplasm and nucleus by transmission electron microscopy proved the intracellular penetration of gadolinium.</p><p><b>CONCLUSIONS</b>hCPPs can be used as an effective vector for an MRI molecular probe to assess the activity of MMP-2.</p>

Coronary artery disease diagnosis with 64-slice spiral CT coronary artery angiography in China and abroad: a meta analysis / 中华心血管病杂志

<p><b>OBJECTIVE</b>This meta-analysis evaluated the accuracy of diagnosing coronary artery disease using 64-section spiral computed tomography, and compared the difference between Chinese studies and abroad studies.</p><p><b>METHODS</b>Relevant English and Chinese articles published from 1998 to 2009 were searched in Cochrane library, Medline, Embase database, OVID database and CNKI. Heterogeneity was tested, pooled weighted sensitivity and specificity and the corresponding 95%CI were calculated. Summary receiver operating characteristic (SROC) curve was drawn and the area under the curve was calculated, differences between studies from China and abroad were compared.</p><p><b>RESULTS</b>A total of 433 articles were searched and 108 articles were included (46 English articles and 62 Chinese articles) after excluding articles of research purposes or design does not match. Because of no gold standard, no blind, can not be calculated literature data, 7 and 20 (P > 0.05), 44 and 6 (P < 0.05), 3 and 1 (P < 0.05) Chinese studies and English articles respectively were excluded. Twenty-seven articles fulfilled all inclusion criteria (8 Chinese and 19 foreign studies) In 8 Chinese studies the pooled weighted sensitivity and specificity and area under SROC curve was 0.892 (95%CI: 0.868 - 0.913), 0.972 (95%CI: 0.966 - 0.977) and 0.983 (95%CI: 0.966 - 1.000) at segment-based analysis. In 19 foreign studies, the pooled weighted sensitivity and specificity and area under SROC curve was 0.971(95%CI: 0.957 - 0.982), 0.878 (95%CI: 0.852 - 0.902) and 0.973 (95%CI: 0.958 - 0.989) at patient-based analysis, 0.917 (95%CI: 0.895 - 0.936), 0.919 (95%CI: 0.909 - 0.928) and 0.974 (95%CI: 0.964 - 0.984) at vessel-based analysis, 0.882 (95%CI: 0.868 - 0.895), 0.959 (95%CI: 0.956 - 0.962) and 0.985 (95%CI: 0.978 - 0.992) at segment-based analysis. Pooled weighted pecificity of 64-section spiral CT angiography at segment-based analysis has significant different between home and abroad (P < 0.05).</p><p><b>CONCLUSIONS</b>Meta-analysis showed that noninvasive 64-section spiral computed tomography could correctly diagnose coronary artery disease with high sensitivity and specificity. Quality of related studies performed in abroad is significantly higher than those performed in China.</p>

Predicting value of various clinical probability scores for diagnosis of lower limb deep venous thrombosis in Chinese patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the predicting value of Wells, Kahn, St. André and Constans scores for the diagnosis of deep venous thrombosis in Chinese patients.</p><p><b>METHODS</b>A total of 274 patients suspected with deep venous thrombosis was prospectively blinded evaluated with the four clinical-score systems. Sensitivity, specificity, positive predictive value, negative predictive value and receiver operation curves were calculated for four clinical scores according sonography results.</p><p><b>RESULTS</b>Sonography evidenced deep venous thrombosis in 88 out of 274 patients. The sensitivity, specificity, positive predictive value and negative predictive value was 77.3%, 65.6%, 51.5% and 85.9%, respectively, for Wells score; 58%, 55.9%, 38.3% and 73.8%, respectively, for Kahn score; 64.8%, 55.4%, 40.7% and 76.9%, respectively, for St. André score and 86.4%, 37.6%, 39.6% and 85.4%, respectively, for Constans score. ROC was 0.761 for Wells score, which was similar as that of Constans score (0.759), then followed by St. André score (0.627) and Kahn score (0.591).</p><p><b>CONCLUSION</b>Our results showed that Wells score and Constans score are superior to Kahn score or St. André score for diagnosing patients with suspected deep venous thrombosis in terms of sensitivity, negative prediction value and ROC values.</p>

Diffusion characteristics of subcortical structures in patients with subcortical ischemic vascular disease and its correlation to cognitive function / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the diffusion-tensor imaging (DTI) characteristics of normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) on conventional magnetic resonance imaging (MRI) in patients with subcortical ischemic vascular disease (SIVD) and examine the relation of such features with the general cognitive function of the patients.</p><p><b>METHODS</b>DTI was performed in 46 SIVD patients and 34 age-matched control subjects with normal MRI findings. The apprarent diffusion coeeficient (ADC) and fractional anisotropy (FA) were measured within the regions of white matter lesions (WMLs), NAWM and NAGM. All the subjects were examined by neurologists with MMSE and clinical neurologic examination.</p><p><b>RESULTS</b>Compared with normal controls, SIVD subjects showed increased ADC values in the subcortical NAGM and NAWM in anterior periventricular and centrum semiovale, with decreased FA values in the caudate nucleus, thalamus and centrum semiovale. An increased severity of the WMLs was associated with increased ADC and decreased FA in the NAWM of SIVD patients. After controlling for age, the ADC in the NAWM of the posterior periventricular, NAWM and WMLs in the centrum semiovale, caudate nucleus and thalamus showed significant inverse correlations to MMSE; FA values in NAWM of the anterior periventricular and WMLs of the centrum semiovale were positively correlated to MMSE.</p><p><b>CONCLUSION</b>In SIVD patients, the NAWM and NAGM regions shown by MRI contain diffusion abnormalities, and these abnormalities shown by DTI are significantly correlated to the general cognitive function of the patients.</p>

Construction of a phage antibody library and screening of anti-epidermal growth factor receptor variant III single chain antibody / 南方医科大学学报

<p><b>OBJECTIVE</b>To obtain specific anti-epidermal growth factor receptor variant III (EGFRvIII) single chain antibody (ScFv) by phage antibody library display system.</p><p><b>METHODS</b>The total RNA was extracted from the spleen B cells of BALB/c mice immunized with pep-3-OVA protein, and the first-strand cDNA was synthesized by reverse transcription. Antibody VH and VL gene fragments were amplified and joined to a ScFv gene with the linker. The ScFv gene was ligated into the phagemid vector pCANTAB5E, which was transformed into competent E. coli TG1. The transformed cells were then infected with M13KO7 helper phage to yield the recombinant phage to construct the phage ScFv library. Pep-3-BSA protein was used to screen the phage antibody library and ELISA carried out to characterize the activity of the antibody.</p><p><b>RESULTS</b>The VH and VL gene fragments of the antibody were about 350 bp and 320 bp in length as analyzed by agarose gel electrophoresis. The ScFv gene was 780 bp, consistent with the expected length. The recombinant phagemid with ScFv gene insert was rescued, and an immune phage ScFv library with the content of 5.0x10(6) was constructed. The recombinant ScFv phage had a titer of 3.0x10(4) cfu/ml, and the fourth phage harvest yielded 56 times as much as that of the first one. SDS-PAGE demonstrated a molecular mass of the soluble ScFv of about 28 kD. ELISA results indicated good specificity of the ScFv to bind EGFRvIII.</p><p><b>CONCLUSION</b>An immune phage ScFv library is successfully constructed, and the ScFv antibody fragment is capable of specific binding to EGFRvIII.</p>

Changes in functional connectivity of ventral anterior cingulate cortex in heroin abusers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies with animal experiments, autopsy, structural magnetic resonance imaging (MRI) and task-related functional MRI (fMRI) have confirmed that brain functional connectivity in addicts has become impaired. The goal of this study was to investigate the alteration of resting-state functional connectivity of the ventral anterior cingulate cortex (vACC) in the heroin abusers' brain.</p><p><b>METHODS</b>Fifteen heroin abusers and fifteen matched healthy volunteers were studied using vACC as the region-of interest (ROI) seed. A 3.0 T scanner with a standard head coil was the imagining apparatus. T2*-weighted gradient-echo planar imaging (GRE-EPI) was the scanning protocol. A ROI seed based correlation analysis used a SPM5 software package as the tool for all images processing.</p><p><b>RESULTS</b>This study showed a functional connection to the insula vACC in heroin abusers. Compared with controls, heroin users showed decreased functional connectivity between the nucleus accumbens (NAc) and vACC, between the parahippocampala gyrus/amgdala (PHC/amygdala) and vACC, between the thalamus and vACC, and between the posterior cingulated cortex/precuneus (PCC/pC) and vACC.</p><p><b>CONCLUSION</b>The altered resting-state functional connectivity to the vACC suggests the neural circuitry on which the addictive drug has an affect and reflects the dysfunction of the addictive brain.</p>

Value of combined wells score and D-dimer test on diagnosing patients with deep venous thrombosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the value of Wells score or/and D-dimer test on diagnosing or excluding deep venous thrombosis (DVT).</p><p><b>METHODS</b>Patients with suspected DVT were retrospectively analyzed. All patients underwent clinical assessment, D-dimer assay and bilateral lower extremity compression sonography within 48 hours of admission. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing DVT by Wells score, D-dimer test, and combined Wells score and D-dimer were compared.</p><p><b>RESULTS</b>A total of 274 patients were analyzed. If low probability was defined as negative and moderate and high probabilities were defined as positive, the sensitivity, specificity, PPV and NPV of the Wells score were 78.4%, 66.1%, 52.3% and 86.6%, respectively. At a cut-off of 500 microg/L, the sensitivity, specificity, PPV and NPV of D-dimer test were 73.9%, 66.1%, 50.8% and 84.2%, respectively. If low probability and D-dimer < 500 microg/L were defined as negative, moderate and high probabilities and D-dimer > or = 500 microg/L were defined as positive, the sensitivity, specificity, PPV and NPV of the combined Wells score and D-dimer test were 88.3%, 76.8%, 67.1% and 92.5%, respectively.</p><p><b>CONCLUSION</b>For clinical suspected DVT patients, DVT diagnosis could be reliably obtained by combined Wells score and D-dimer test.</p>

A Meta-Analysis of the Accuracy of Prostate Cancer Studies Which Use Magnetic Resonance Spectroscopy as a Diagnostic Tool

OBJECTIVE: We aimed to do a meta-analysis of the existing literature to assess the accuracy of prostate cancer studies which use magnetic resonance spectroscopy (MRS) as a diagnostic tool. MATERIALS AND METHODS: Prospectively, independent, blind studies were selected from the Cochrane library, Pubmed, and other network databases. The criteria for inclusion and exclusion in this study referenced the criteria of diagnostic research published by the Cochrane center. The statistical analysis was adopted by using Meta-Test version 6.0. Using the homogeneity test, a statistical effect model was chosen to calculate different pooled weighted values of sensitivity, specificity, and the corresponding 95% confidence intervals (95% CI). The summary receiver operating characteristic (SROC) curves method was used to assess the results. RESULTS: We chose two cut-off values (0.75 and 0.86) as the diagnostic criteria for discriminating between benign and malignant. In the first diagnostic criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI (expressed as area under curve [AUC]) were 0.82 (0.73, 0.89), 0.68 (0.58, 0.76), and 83.4% (74.97, 91.83). In the second criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI were 0.64 (0.55, 0.72), 0.86 (0.79, 0.91) and 82.7% (68.73, 96.68). CONCLUSION: As a new method in the diagnostic of prostate cancer, MRS has a better applied value compared to other common modalities. Ultimately, large scale RCT (randomized controlled trial) randomized controlled trial studies are necessary to assess its clinical value.

Intercellular imaging by a polyarginine derived cell penetrating peptide labeled magnetic resonance contrast agent, diethylenetriamine pentaacetic acid gadolinium / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cellular plasma membrane represents a natural barrier to many exogenous molecules including magnetic resonance (MR) contrast agent. Cell penetrating peptide (CPP) is used to internalize proteins, peptides, and radionuclide. This study was undertaken to assess the value of a new intracellular MR contrast medium, CPP labeled diethylenetriamine pentaacetic acid gadolinium (Gd-DTPA) in molecular imaging in vitro.</p><p><b>METHODS</b>Fluorescein-5-isothiocyanate (FITC) and Gd-DTPA respectively labeled with CPP (FITC-CPP, Gd-DTPA-CPP) were synthesized by the solid-phase method. Human hepatic cancer cell line-HepG2 was respectively stained by FITC-CPP and FITC to observe the uptake and intracellular distribution. HepG2 was respectively incubated with 100 nmol/ml Gd-DTPA-CPP for 0, 10, 30, 60 minutes, and imaged by MR for studying the relationship between the incubation time and T(1)WI signal. The cytotoxicity to NIH3T3 fibroblasts cells was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay (MTT).</p><p><b>RESULTS</b>The molecular weights of CPP labeled imaging agents, which were determined by MALDI mass spectrometry (FITC-CPP MW = 2163.34, Gd-DTPA-CPP MW = 2285.99), were similar to the calculated molecular weights. Confocal microscopy suggested HepG2 translocated FITC-CPP in cytoplasm and nucleus independent with the incubation temperature. MR images showed HepG2 uptaken Gd-DTPA-CPP had a higher T(1) weighted imaging (T(1)WI) signal, and that the T(1)WI signal intensity was increasing in a time-dependent manner (r = 0.972, P = 0.001), while the signal intensity between the cells incubated by Gd-DTPA for 60 minutes and the controlled cells was not significantly different (P = 0.225). By MTT, all concentrations from 50 nmol/ml to 200 nmol/ml had no significant (F = 0.006, P = 1.000) effect on cell viability of mouse NIH3T3 fibroblasts, compared with the control group.</p><p><b>CONCLUSIONS</b>The newly constructed CPP based on polyarginine can translocate cells by carrying FITC and MR contrast agent Gd-DTPA, and the intracellular concentrations are readily detectable by MR imaging, suggesting a new way for MR molecular imaging.</p>

The situation and countermeasure of medical measurements / 中国医疗器械杂志

This paper introduces the significance, the present development situation and some suggestions of the medical measurements.

Pulmonary functional MRI: an animal model study of oxygen-enhanced ventilation combined with Gd-DTPA-enhanced perfusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The assessment of regional pulmonary ventilation and perfusion is essential for the evaluation of a variety of lung disorders. Pulmonary ventilation MRI using inhaled oxygen as a contrast medium can be obtained with a clinical MR scanner, without additional equipment, and has been demonstrated to be a feasible means of assessing ventilation in animal models and some clinical patients. However, few studies have reported on MR ventilation-perfusion imaging. In this study, we evaluated the usefulness of oxygen-enhanced ventilation in combination with first-pass Gd-DTPA-enhanced perfusion MRI in a canine model of pulmonary embolism and airway obstruction.</p><p><b>METHODS</b>Peripheral pulmonary embolisms were produced in eight dogs by intravenous injection of gelfoam strips at the pulmonary segmental arterial level, and airway obstructions were created in five of the dogs by inserting a self-designed balloon catheter into a secondary bronchus. Oxygen-enhanced MR ventilation images were produced by subtracting images from before and after inhalation of pure oxygen. Pulmonary perfusion MR images were acquired with a dynamic three-dimensional fast gradient-echo sequence. MR ventilation and perfusion images were read and contrasted with results from general examinations of pathological anatomy, ventilation-perfusion scintigraphy, and pulmonary angiography.</p><p><b>RESULTS</b>Regions identified as having airway obstructions matched using both MR ventilation and perfusion imaging, but regions of pulmonary embolisms were mismatched. The area of airway obstruction defects was smaller using MR ventilation imagery than that using ventilation scintigraphy. Abnormal perfusion regions due to pulmonary embolisms were divided into defective regions and reduced regions based on the time course of signal intensity changes. In the diagnosis of pulmonary embolisms with the technique of ventilation and perfusion MRI, sensitivity and specificity were 75.0% and 98.1%, respectively, and the diagnostic results of this MRI technique were in agreement with the results of ventilation-perfusion scintigraphy and pulmonary angiography (K: 0.899, 0.743).</p><p><b>CONCLUSIONS</b>Oxygen-enhanced ventilation in combination with pulmonary perfusion MRI can be used to diagnose abnormalities of airways and blood vessels in the lungs, and can provide regional functional information with high spatial and temporal resolution. This method possesses great potential value for clinical applications.</p>