Structural connectivity from DTI to predict mild cognitive impairment in de novo Parkinson's disease.

BACKGROUND: Early detection of Parkinson's disease (PD) patients at high risk for mild cognitive impairment (MCI) can help with timely intervention. White matter structural connectivity is considered an early and sensitive indicator of neurodegenerative disease. OBJECTIVES: To investigate whether baseline white matter structural connectivity features from diffusion tensor imaging (DTI) of de novo PD patients can help predict PD-MCI conversion at an individual level using machine learning methods. METHODS: We included 90 de novo PD patients who underwent DTI and 3D T1-weighted imaging. Elastic net-based feature consensus ranking (ENFCR) was used with 1000 random training sets to select clinical and structural connectivity features. Linear discrimination analysis (LDA), support vector machine (SVM), K-nearest neighbor (KNN) and naïve Bayes (NB) classifiers were trained based on features selected more than 500 times. The area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN) and specificity (SPE) were used to evaluate model performance. RESULTS: A total of 57 PD patients were classified as PD-MCI nonconverters, and 33 PD patients were classified as PD-MCI converters. The models trained with clinical data showed moderate performance (AUC range: 0.62-0.68; ACC range: 0.63-0.77; SEN range: 0.45-0.66; SPE range: 0.64-0.84). Models trained with structural connectivity (AUC range, 0.81-0.84; ACC range, 0.75-0.86; SEN range, 0.77-0.91; SPE range, 0.71-0.88) performed similar to models that were trained with both clinical and structural connectivity data (AUC range, 0.81-0.85; ACC range, 0.74-0.85; SEN range, 0.79-0.91; SPE range, 0.70-0.89). CONCLUSIONS: Baseline white matter structural connectivity from DTI is helpful in predicting future MCI conversion in de novo PD patients.

Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

Development and Validation of a Deep Learning and Radiomics Combined Model for Differentiating Complicated From Uncomplicated Acute Appendicitis.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a deep learning and radiomics combined model for differentiating complicated from uncomplicated acute appendicitis (AA). MATERIALS AND METHODS: This retrospective multicenter study included 1165 adult AA patients (training cohort, 700 patients; validation cohort, 465 patients) with available abdominal pelvic computed tomography (CT) images. The reference standard for complicated/uncomplicated AA was the surgery and pathology records. We developed our combined model with CatBoost based on the selected clinical characteristics, CT visual features, deep learning features, and radiomics features. We externally validated our combined model and compared its performance with that of the conventional combined model, the deep learning radiomics (DLR) model, and the radiologist's visual diagnosis using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of our combined model in distinguishing complicated from uncomplicated AA was 0.816 (95% confidence interval [CI]: 0.785-0.844). In the validation cohort, our combined model showed robust performance across the data from three centers, with AUCs of 0.836 (95% CI: 0.785-0.879), 0.793 (95% CI: 0.695-0.872), and 0.723 (95% CI: 0.632-0.802). In the total validation cohort, our combined model (AUC = 0.799) performed better than the conventional combined model, DLR model, and radiologist's visual diagnosis (AUC = 0.723, 0.755, and 0.679, respectively; all P < 0.05). Decision curve analysis showed that our combined model provided greater net benefit in predicting complicated AA than the other three models. CONCLUSION: Our combined model allows the accurate differentiation of complicated and uncomplicated AA.

Prognostic Impact of Quantifying Sarcopenia and Adipopenia by Chest CT in Severe Aplastic Anemia Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation.

RATIONALE AND OBJECTIVES: To investigate the prognostic role of chest CT-defined sarcopenia and adipopenia in severe aplastic anemia (SAA) patients treated with hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: This was a retrospective study of 123 consecutive SAA patients treated with HSCT. CT imaging was performed to quantify the pectoralis muscle (including major and minor) index (PMI) and the corresponding subcutaneous adipose tissue index (SAI). Sarcopenia and adipopenia were defined as PMI and SAI lower than the respective sex-specific medians. Correlations of the PMI and SAI with anthropometric indexes were calculated. Transplant-related outcomes were compared between the sarcopenia and adipopenia groups. Prognostic factors for overall survival (OS) and fail-free survival (FFS) were identified by Cox regression and were used to create a nomogram. The accuracy of the nomogram was evaluated by ROC curves. RESULTS: PMI showed good correlation with BMI and fat-free mass index (p < 0.001). SAI correlated with BMI and fat mass index (p < 0.001). The sarcopenia group (47.2%) had a significantly worse 3-year OS (90.8% vs. 77.6%, p = 0.045) and 3-year FFS (89.2% vs. 74.1%, p = 0.035) than the nonsarcopenia group. Sarcopenia status and diagnostic category were used to construct the nomogram of OS, as these were independent prognostic factors in the multivariate analysis for OS and FFS (p < 0.05). The area under the curve of the nomogram at one year and three years was 0.801 and 0.721, respectively. CONCLUSION: Sarcopenia indicates a poor prognosis in SAA patients undergoing HSCT. Intensive supportive care is suggested for SAA patients with sarcopenia before transplantation.

Baseline cerebral structural morphology predict freezing of gait in early drug-naïve Parkinson's disease.

Freezing of gait (FOG) greatly impacts the daily life of patients with Parkinson's disease (PD). However, predictors of FOG in early PD are limited. Moreover, recent neuroimaging evidence of cerebral morphological alterations in PD is heterogeneous. We aimed to develop a model that could predict the occurrence of FOG using machine learning, collaborating with clinical, laboratory, and cerebral structural imaging information of early drug-naïve PD and investigate alterations in cerebral morphology in early PD. Data from 73 healthy controls (HCs) and 158 early drug-naïve PD patients at baseline were obtained from the Parkinson's Progression Markers Initiative cohort. The CIVET pipeline was used to generate structural morphological features with T1-weighted imaging (T1WI). Five machine learning algorithms were calculated to assess the predictive performance of future FOG in early PD during a 5-year follow-up period. We found that models trained with structural morphological features showed fair to good performance (accuracy range, 0.67-0.73). Performance improved when clinical and laboratory data was added (accuracy range, 0.71-0.78). For machine learning algorithms, elastic net-support vector machine models (accuracy range, 0.69-0.78) performed the best. The main features used to predict FOG based on elastic net-support vector machine models were the structural morphological features that were mainly distributed in the left cerebrum. Moreover, the bilateral olfactory cortex (OLF) showed a significantly higher surface area in PD patients than in HCs. Overall, we found that T1WI morphometric markers helped predict future FOG occurrence in patients with early drug-naïve PD at the individual level. The OLF exhibits predominantly cortical expansion in early PD.

Disrupted Brain Structural Network Connection in de novo Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder.

Objective: To explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD). Materials and Methods: This study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group. Results: All three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients. Conclusions: PD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.

Type 2 diabetes prevention diet and the risk of pancreatic cancer: A large prospective multicenter study.

BACKGROUND & AIMS: Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. METHODS: A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. RESULTS: After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4versus1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend = 0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4versus1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4versus1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction = 0.095). CONCLUSIONS: Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.

Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice.

Atherosclerosis is a serious age-related pathology, and one of its hallmarks is the presence of chronic inflammation. Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is a cholesterol sensor that plays an essential role in regulating intracellular cholesterol homeostasis. Accordingly, dysregulation of the SCAP-SREBP pathway has been reported to be closely associated with an increased risk of obesity, hypercholesterolemia, and cardiovascular disease. In this study, we explored whether sterol-resistant SCAP (D443N mutation) in vascular smooth muscle cells (VSMCs) of mice promotes vascular inflammation and accelerates the occurrence and progression of atherosclerosis. We established a transgenic knock-in mouse model of atherosclerosis with an activating D443N mutation at the sterol-sensing domain of SCAP (SCAPD443N) by microinjection. Next, SCAPD443N/ApoE-/- mice were generated by crossing SCAPD443N mice with apolipoprotein E-/- (ApoE-/-) background mice. We found that sterol-resistant SCAP markedly amplified and accelerated the progression of atherosclerotic plaques in SCAPD443N/ApoE-/- mice compared with that in control ApoE-/- mice. Similarly, in SCAPD443N mice, aortic atherosclerotic plaques both appeared earlier and were greater in number than that in control SCAP+/+ mice, both of which were fed a Western diet for 12 or 24 weeks. Moreover, we observed that sterol-resistant SCAP significantly increased local inflammation and induced endothelial dysfunction in the aortas of SCAPD443N mice and SCAPD443N/ApoE-/- mice. In vitro, we also found that sterol-resistant SCAP overexpression in VSMCs increased the release of inflammatory cytokines and induced endothelial cell injury when both cell types were cocultured. Furthermore, we demonstrated that sterol-resistant SCAP overexpression in VSMCs promoted SCAP and NLRP3 inflammasome cotranslocation to the Golgi and increased the activation of the NLRP3 inflammasome pathway. These findings suggested that sterol-resistant SCAP in VSMCs of mice induced vascular inflammation and endothelial dysfunction, consequently accelerating atherosclerosis by activating the NLRP3 inflammasome pathway.

Prediction of Microvascular Invasion in Hepatocellular Carcinoma With a Multi-Disciplinary Team-Like Radiomics Fusion Model on Dynamic Contrast-Enhanced Computed Tomography.

OBJECTIVE: To investigate microvascular invasion (MVI) of HCC through a noninvasive multi-disciplinary team (MDT)-like radiomics fusion model on dynamic contrast enhanced (DCE) computed tomography (CT). METHODS: This retrospective study included 111 patients with pathologically proven hepatocellular carcinoma, which comprised 57 MVI-positive and 54 MVI-negative patients. Target volume of interest (VOI) was delineated on four DCE CT phases. The volume of tumor core (V tc ) and seven peripheral tumor regions (V pt , with varying distances of 2, 4, 6, 8, 10, 12, and 14 mm to tumor margin) were obtained. Radiomics features extracted from different combinations of phase(s) and VOI(s) were cross-validated by 150 classification models. The best phase and VOI (or combinations) were determined. The top predictive models were ranked and screened by cross-validation on the training/validation set. The model fusion, a procedure analogous to multidisciplinary consultation, was performed on the top-3 models to generate a final model, which was validated on an independent testing set. RESULTS: Image features extracted from V tc +V pt(12mm) in the portal venous phase (PVP) showed dominant predictive performances. The top ranked features from V tc +V pt(12mm) in PVP included one gray level size zone matrix (GLSZM)-based feature and four first-order based features. Model fusion outperformed a single model in MVI prediction. The weighted fusion method achieved the best predictive performance with an AUC of 0.81, accuracy of 78.3%, sensitivity of 81.8%, and specificity of 75% on the independent testing set. CONCLUSION: Image features extracted from the PVP with V tc +V pt(12mm) are the most reliable features indicative of MVI. The MDT-like radiomics fusion model is a promising tool to generate accurate and reproducible results in MVI status prediction in HCC.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

Differences in Clinical and Imaging Presentation of Pediatric Patients with COVID-19 in Comparison with Adults.

PURPOSE: To characterize and compare the initial clinical and imaging features of coronavirus disease 2019 (COVID-19) in pediatric and adult patients undergoing chest CT. MATERIALS AND METHODS: A total of 61 patients, consisting of 47 adults (aged 18 years or older) and 14 pediatric patients (aged younger than 18 years) with laboratory-confirmed COVID-19 confirmed by real-time reverse-transcription polymerase chain reaction between January 25 and February 15, 2020, were enrolled in this study. All patients underwent chest CT within 3 days after the initial reverse transcription polymerase chain reaction test. The clinical presentation, serum markers, and CT findings were assessed and compared between the adult and pediatric patients. RESULTS: Fever was less common in pediatric patients than in adults (six of 14, 42.9% vs 39 of 47, 83%; P = .008). Leukopenia or normal, lymphopenia or normal, and increased or normal C-reactive protein level were common in both groups with no difference (P > .05). Compared with the adults, pediatric patients had a lower rate of positive CT findings and a milder clinical grade (P = .004 and P = .001, respectively). At chest CT, the number of pulmonary lobes involved was found to be reduced in pediatric patients when compared with adults (P = .012). Subpleural distribution of lung opacities was a dominant feature in both groups, whereas bronchial distribution was more common in the pediatric group (P = .048). Among the CT features in adults, ground-glass opacities (GGOs) were the most common finding (24 of 43, 53.5%), followed by GGO with consolidation (14 of 43, 27.9%). In pediatric patients, GGOs accounted for 42.9% (three of seven), bronchial wall thickening occurred in 28.6% (two of seven), and GGOs with consolidations and nodular opacities occurred in 14.3% (one of seven). However, these CT features did not differ in the two groups, except for bronchial wall thickening, which was more commonly found in pediatric patients (P = .048). In addition, the semiquantitative scores of lung involvement were higher in adults than in pediatric patients (8.89 ± 4.54 vs 1.86 ± 2.41; P < .001). CONCLUSION: Compared with adults, pediatric patients with COVID-19 showed distinctive clinical and CT features. Pediatric patients tend to have milder clinical symptoms, fewer positive results at CT, and less extensive involvement at imaging. Bronchial wall thickening was relatively more frequent on CT images from pediatric patients with COVID-19 in comparison with adults.Supplemental material is available for this article.© RSNA, 2020.

SCAP knockdown in vascular smooth muscle cells alleviates atherosclerosis plaque formation via up-regulating autophagy in ApoE-/- mice.

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a cholesterol sensor that plays a critical role in regulating intracellular cholesterol levels, but the association between SCAP and foam cell formation in vascular smooth muscle cells (VSMCs) is poorly understood. Using tissue-specific SCAP knockdown in apolipoprotein E (ApoE)-/- mice, we sought to search the mechanism through which SCAP signaling affects VSMC foam cell development. VSMC-specific SCAP knockdown mice were generated by Cre/LoxP-mediated gene targeting in ApoE-/- mice. Breeding SCAPflox/flox mice with SM22α-Cre mice resulted in no viable offspring with the homozygote SM22-Cre: SCAPflox/flox genotype due to embryonic lethality. We found that the heterozygote SM22α-Cre:SCAPflox/+:ApoE-/- mice fed a Western diet for 12 wk had significantly fewer atherosclerotic plaques in their aortas than the control mice due to reduced cholesterol uptake and synthesis. Furthermore, we found that autophagy in VSMCs was increased in SM22α-Cre:SCAPflox/+:ApoE-/- mice. Similarly, in vitro, SCAP knockdown in human coronary artery VSMCs by RNA interference reduced lipid accumulation and increased autophagy under LDL cholesterol loading. SCAP knockdown in VSMCs reduced oxidative stress and increased AMPK phosphorylation, which contributed to the up-regulation of autophagy in vivo and in vitro. VSMC-specific SCAP knockdown decreased the lipid accumulation and intracellular oxidative stress, increased excessive lipid clearance by enhancing lipid autophagy mediated by the reactive oxygen species/AMPK pathway in VSMCs, and consequently alleviated atherosclerosis plaque formation.-Li, D., Chen, A., Lan, T., Zou, Y., Zhao, L., Yang, P., Qu, H., Wei, L., Varghese, Z., Moorhead, J. F., Chen, Y., Ruan, X. Z. SCAP knockdown in vascular smooth muscle cells alleviates atherosclerosis plaque formation via up-regulating autophagy in ApoE-/- mice.

Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration.

[Binding of glycoprotein ß2-GPI with oxidized low density lipoprotein].

We analyzed the binding of P.rß2-GPI-DV with ox-LDL by fluorescence, molecular simulation and circular dichroism. We used SDS-PAGE and Western blotting to identify the purity of P.rß2-GPI-DV, fluorescence, circular dichroism spectroscopy and molecular docking simulation to analyze the binding between P.rß2-GPI-DV and oxLDL. P.rß2-GPI-DV was specifically recognized by anti-His antibody at 12 kDa position. The chromophoric groups, the changes of secondary structure and the molecular docking simulations revealed that the active pocket formed by Cys281-Lys-Asn-Lys-Glu-Lys-Lys287 and Leu313-Ala-Phe-Trp316 of P.rß2-GPI-DV and the -COOH carboxyl of oxLig-1 were the key for binding. P.rß2-GPI combined with ox-LDL via the fifth functional domain and the -COOH group. Our findings provide theoretical basis to further study the binding between ß2-GPI and ox-LDL in serum.

Sex Differences in Hazard Ratio During Drug Treatment of Non-small-cell Lung Cancer in Major Clinical Trials: A Focused Data Review and Meta-analysis.

PURPOSE: Understanding how sex impacts the efficacy of anticancer agents is a crucial step toward personalized and precision medicine. This review and meta-analysis evaluated sex differences in hazard ratios (HRs) of progression-free survival and overall survival in representative Phase III clinical trials of non-small-cell lung cancer (NSCLC). METHODS: Data were extracted from 24 large-scale clinical trials that included 12,000 male and 7000 female patients. The data were examined for HR differences between subgroups by sex, smoking status, and age, and for potential sex-smoking status, sex-age, and sex-drug interactions, during cancer treatment. FINDINGS: Summarized information revealed variations in the influences of sex, smoking status, and age on the efficacy of drugs used for the treatment of NSCLC. The male and female subgroups had different HR values. Smoking status, age, and the percentage of female patients in a treatment group had no influence on the sex HR. The sex difference was supported by a set of data collected from all journals. IMPLICATIONS: The findings from this meta-analysis are important for assessing potential toxicity during drug treatment in both sexes. The outcomes measures of a drug in clinical application should be specified by subpopulation, such as males versus females, as a first step in personalized medicine.

Differentiation of central lung cancer from atelectasis: comparison of diffusion-weighted MRI with PET/CT.

OBJECTIVE: Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. MATERIALS AND METHODS: 38 consecutive lung cancer patients (26 males, 12 females; age range: 28-71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm(2). RESULTS: PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm(2)/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). CONCLUSIONS: DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer.

[Study on the polymorphism of killer cell immunoglobulin like receptor (KIR) gene with systemic lupus erythematosus of North population in China].

AIM: To investigate the polymorphism of KIR genes in systemic lupus erythematosus (SLE) patients, and to study the correlation between KIR genes and susceptibility of SLE. METHODS: The polymorphism of KIR genes were detected by PCR-SSP technique in 62 patients with SLE and 61 healthy persons as controls from North of China. RESULTS: The differences of KIR frequency between the SLE group and the control were tested by statistical analysis. The most frequent genotype was KIR 3DP1, 2DL1, 2DP1, 3DL1, 2DL3, 1D, followed by 2DS4, 2DL5, 3DS1, 2DS2, 2DS5 and 2DL2. KIR 2DS1, 2DS3 and 3DP1v were lower in frequency compared with others. The frequency of KIR 3DS1, 2DL2, 2DL5 and 2DL3 were significantly lower in SLE group than that in the control èP<0.01é. CONCLUSION: There may be a association between the polymorphism of KIR genes with SLE in North of China should be investigated further.

Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis.

Cyclin B1, a key component in the control of cell cycle progression from G(2) to M phase, has been implicated in tumorigenesis and the development of malignancy. However, the underlying mechanism by which cyclin B1 acts as an important oncogenic molecule remains largely unknown. Here we show that ectopic expression of cyclin B1 promotes cell proliferation, enhances cell motility and migration and results in increased ability of cells extravasating through the capillary endothelium. Interestingly, isogenic esophageal squamous cell carcinoma (ESCC) cells overexpressing cyclin B1 reveal strong invasive growth and high potential of metastasis to lung in xenograft mice. Suppression of cyclin B1 expression via small interfering RNA approach in high-metastatic esophagus carcinoma cells specifically inhibits their ability to metastasize from the primary ESCC to lung. Notably, altered expression of epithelial markers and mesenchymal markers were observed in the cells overexpressing cyclin B1, suggesting that cyclin B1 contributes to metastasis probably by promoting an epithelial-mesenchymal transition. These results establish a mechanistic link between cyclin B1 and ESCC metastasis and provide novel insight into understanding of cyclin B1 in the development of ESCC malignancy.