Graphene/SnS2 van der Waals Photodetector with High Photoresponsivity and High Photodetectivity for Broadband 365-2240 nm Detection.

The fabrication of graphene/SnS2 van der Waals photodetectors and their photoelectrical properties are systematically investigated. It was found that a dry transferred graphene/SnS2 van der Waals heterostructure had a broadband sensing range from ultraviolet (365 nm) to near-infrared (2.24 µm) and respective improved responsivities and photodetectivities of 7.7 × 103 A/W and 8.9 × 1013 jones at 470 nm and 2 A/W and 1.8 × 1010 jones at 1064 nm. Moreover, positive and negative photoconductance effects were observed when the photodetectors were illuminated by photon sources with energies greater and smaller than the bandgap of SnS2, respectively. The photoresponsivity (R) versus incident power density (P) follows the empirical law R ∝ Pinß, with ß > -1 for positive photoconductance effects and ß < -1 for negative photoconductance effects. On the basis of the Fowler-Nordheim tunneling model and a Poisson and drift-diffusion simulation, we show quantitatively that the barrier height and barrier width of the heterostructure photodetector could be controlled by a laser and an external electrical field through a photogating effect generated by carriers trapped at the interface, which could be used to tune the separation and transport of photogenerated carriers. Our results may be useful for the design of high performance van der Waals heterojunction photodetectors.

Clinical and microbiological characteristics of patients with biliary disease.

BACKGROUND: Biliary diseases are common digestive system disorders which may combine with biliary tract infection such as cholecystitis or cholangitis. Thus, rapid identification of the bacteria and their antibiotic susceptibility profiles are crucial for reducing the mortality of patients with biliary tract infection. AIM: To identify bacterial species and antibiotic susceptibility for antibacterial therapy and analyze bile cultivation risk factors for increasing detection rates. METHODS: This retrospective study was conducted from July 2008 to July 2017. In total, 1339 bile samples which were collected during therapeutic endoscopic retrograde cholangiopan-creatography or percutaneous transhepatic cholangiodrainage or other biliary surgeries or biliary drainage were obtained to characterize pathogen spectra, antibiotic susceptibility, and clinical features. Clinical data including age, sex, comorbidities, clinical symptoms, protopathies, and history of biliary tract diseases and surgeries were collated from hospital medical records. Species identification and initial drug susceptibility were further identified by biochemical characterization using the VITEK 2 Compact test. RESULTS: Positive microbiological findings were observed in 738 samples. The most frequently encountered strains were gram-negative bacteria (74.94%), including Escherichia coli (37.78%), Pseudomonas aeruginosa (8.96%), and Klebsiella pneumoniae (10.29%). Bile bacteria were largely sensitive to carbapenems, piperacillin/tazobactam, and gentamicin. Gram-negative strains had low susceptibility to ceftriaxone, quinolones and ampicillin. Almost the same micro-organisms were present in patients with malignant and benign diseases. The number of samples with Klebsiella pneumoniae in the bile culture were significantly different between patients with malignant and benign diseases (55 vs 30; P = 0.019). Age (P < 0.001), fever (P < 0.001), history of biliary tract diseases and surgeries (both P < 0.001), benign disease (P = 0.002), and the comorbidity chronic renal insufficiency (P = 0.007) affected the positive rates of the bile samples. CONCLUSION: Gram-negative bacteria were the most commonly isolated biliary bacteria. We determined the major factors associated with positive detection rates. Microbiological analysis of bile samples allowed accurate antibiotic treatments.

Correlation analysis between metabolic tumor burden measured by positron emission tomography/computed tomography and the 2015 World Health Organization classification of lung adenocarcinoma, with a risk prediction model of tumor spread through air spaces.

BACKGROUND: Tumor spread through air spaces (STAS) is an important pattern of invasion and impacts the frequency and location of recurrence. The objective was to assess the correlation between metabolic tumor burden of positron emission tomography/computed tomography (PET/CT) and 2015 World Health Organization (WHO) classification of lung adenocarcinoma, and to establish a risk prediction model of STAS. METHODS: We reviewed 127 consecutive patients. The SUVmax, SUVmean, SUVpeak, MTV, TLG, diameter, and CTV were measured. All risk factors were analyzed by multivariate logistic regression analysis; regression coefficients and odds ratios were calculated for independent risk factors. A STAS risk prediction model was created using the regression coefficients to determine the predictive probability (PP). RESULTS: The nodule types and SUV were significantly correlated with 2015 WHO pathological categories (P<0.001). Most of (83.3%) the lepidic predominant adenocarcinoma (LPA) appeared as non-solid or part-solid nodules with the lowest SUV (P<0.05). There was a significant difference in STAS distribution among different nodule types (P=0.000). STAS was significantly correlated with SUVmax (P=0.000), SUVmean (P=0.000), SUVpeak (P=0.000), TLG (P=0.001), and diameter (P=0.044). The risk prediction model of STAS was established. The PP of STAS and the incidence of STAS were analyzed using the ROC curve (AUC =0.759, P=0.000). The sensitivity, specificity, and accuracy of the predictive model for STAS were 47.1%, 88.6%, and 71.1%, respectively. CONCLUSIONS: The LPA appeared as non-solid nodule with low SUV without STAS has a good prognosis. SUV and TLG are valuable predictive indices in the prediction of STAS. The predictive model developed in predicting the incidence of STAS has good specificity and accuracy.

Diagnostic accuracy of single-source dual-energy computed tomography and ultrasonography for detection of lateral cervical lymph node metastases of papillary thyroid carcinoma.

BACKGROUND: Dual-energy computed tomography (DECT) imaging can generate iodine-based material decomposition (MD) images and spectral HU curve. This study aimed to investigate the diagnostic accuracy of single-source dual-energy CT (DECT) and ultrasonography (US) for detecting lateral cervical lymph node metastases of papillary thyroid carcinoma (PTC). METHODS: Thirty patients with PTC were enrolled in the study and underwent DECT and US examination before thyroidectomy and cervical lymph node dissection. The spectral parameters included iodine concentration (IC), normalized iodine concentration (NIC) and slope (λHU) of lymph nodes. The CT morphological parameters included maximal short diameter, shape, margin, calcification and cystic degeneration of lymph nodes. The US morphological parameters included maximal short diameter, calcification and cystic degeneration of lymph nodes. The diagnostic value of every single spectral parameter, combined gemstone spectral image (GSI) parameters, CT morphological parameters and US morphological parameters between metastatic and non-metastatic lymph nodes were statistically compared. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were used to determine the diagnostic value. RESULTS: Ninety-nine lymph nodes from thirty patients were pathologically confirmed. Among them, 70 (70.7%) were metastatic. For single GSI parameters, ROC analysis showed that the area under the curve (AUC) for IC was the highest (AUC =0.937) but the difference was not statistically significant when compared with NIC or slope (λHU) (P>0.05). The optimal diagnostic threshold for IC was 2.56 mg/mL, with a sensitivity, specificity and accuracy of 87.1%, 93.1%, and 88.9%, respectively. The AUC for combined GSI parameter (AUC =0.942) was higher compared with the US morphological parameters (AUC =0.771, P<0.001), with a sensitivity, specificity, and accuracy of 92.9%, 86.2%, and 90.9%, respectively. However AUC did not differ significantly among combined GSI parameters, combined CT morphological parameters and a single application for spectral CT parameters IC (P>0.05). CONCLUSIONS: Combined GSI parameters showed better diagnostic accuracy in lateral cervical lymph node metastasis of PTC compared with that of combined US morphological parameters. IC alone showed excellent diagnostic stability and could be performed easily.

TREM-1 Contributes to Inflammation in IgA Nephropathy.

BACKGROUND: Circulating IgA1-containing immune complexes (cIgA1) were shown to play important roles in IgA nephropathy (IgAN). They could induce the release of multiple inflammatory factors, including MCP-1 and IL-6, and elevated urinary inflammatory factors were also reported in patients with IgAN, which suggested that inflammation is a major contributor to kidney injury in IgAN. After the previous identification of the upregulated release of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by mesangial cells under cIgA1 challenge using cytokine array, in the present study, we further explored the role of TREM-1, an amplifier of inflammation, in cIgA1-induced kidney injury. METHODS: In total, 35 patients with IgAN and 17 healthy controls were enrolled. The cIgA1 was isolated from plasma and used to treat cultured mesangial cells. The mRNA expression of TREM-1 as well as levels of sTREM-1, MCP-1, and IL-6 in the mesangial cell supernatant and urine samples were detected. RESULTS: We found that cIgA1 from patients with IgAN could significantly upregulate the expression of TREM-1 in mesangial cells compared to healthy controls. The levels of ΔsTREM-1 were positively correlated with MCP-1 levels in the mesangial supernatant. Similarly, higher urinary levels of sTREM-1 were also observed in patients with IgAN compared to healthy controls. Moreover, IgAN patients with detectable urinary sTREM-1 presented with severe clinical and pathological manifestations, including higher IgA and lower eGFR levels, compared to patients whose urinary sTREM-1 levels were below the limit of quantification. CONCLUSION: Our present study suggested that TREM-1 in cIgA1 induced inflammatory kidney injury in IgAN.

Prevalence and Risk Factors of Acute Pulmonary Embolism in Patients with Lung Cancer Surgery.

Acute pulmonary embolism (PE) is one of the serious complications with high mortality after thoracic surgery. The authors aimed to determine the prevalence of PE events and evaluate additional risk factors for PE in patients with lung cancer surgery. Patients underwent lung cancer resections during January 2012 to July 2015 and had 30-day postoperative follow-up were included. Those with incomplete or miscoded data were excluded. The number of postoperative PE events was recorded retrospectively. Analyses were used to evaluate risk factors of PE during the hospitalization. The authors reviewed 11,474 patients who underwent surgery for lung cancer. The overall 30-day incidence of PE after thoracic surgery at their institution was 0.53%. The 30-day PE incidence without chemical prophylaxis was 0.57% (55/9,726) and the mortality rate was 10%. Multivariate analyses revealed that age over 66 (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05-1.12, p < 0.001), more extensive surgery than lobectomy (OR: 2.34, 95% CI: 1.28-4.25, p = 0.006) and stage IV of lung cancer (OR: 4.22, 95% CI: 1.50-11.9, p = 0.007) were associated with an increased risk of PE. Using these additional risk factors, based on readily available clinical characteristics, can help to risk-stratify patients and warrant extended chemical prophylaxis for patients to reduce the incidence of acute PE.

Diagnostic Performance and Interobserver Consistency of the Prostate Imaging Reporting and Data System Version 2: A Study on Six Prostate Radiologists with Different Experiences from Half a Year to 17 Years / 中华医学杂志(英文版)

<p><b>Background</b>One of the main aims of the updated Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) is to diminish variation in the interpretation and reporting of prostate imaging, especially among readers with varied experience levels. This study aimed to retrospectively analyze diagnostic consistency and accuracy for prostate disease among six radiologists with different experience levels from a single center and to evaluate the diagnostic performance of PI-RADS v2 scores in the detection of clinically significant prostate cancer (PCa).</p><p><b>Methods</b>From December 2014 to March 2016, 84 PCa patients and 99 benign prostatic shyperplasia patients who underwent 3.0T multiparametric magnetic resonance imaging before biopsy were included in our study. All patients received evaluation according to the PI-RADS v2 scale (1-5 scores) from six blinded readers (with 6 months and 2, 3, 4, 5, or 17 years of experience, respectively, the last reader was a reviewer/contributor for the PI-RADS v2). The correlation among the readers' scores and the Gleason score (GS) was determined with the Kendall test. Intra-/inter-observer agreement was evaluated using κ statistics, while receiver operating characteristic curve and area under the curve analyses were performed to evaluate the diagnostic performance of the scores.</p><p><b>Results</b>Based on the PI-RADS v2, the median κ score and standard error among all possible pairs of readers were 0.506 and 0.043, respectively; the average correlation between the six readers' scores and the GS was positive, exhibiting weak-to-moderate strength (r = 0.391, P = 0.006). The AUC values of the six radiologists were 0.883, 0.924, 0.927, 0.932, 0.929, and 0.947, respectively.</p><p><b>Conclusion</b>The inter-reader agreement for the PI-RADS v2 among the six readers with different experience is weak to moderate. Different experience levels affect the interpretation of MRI images.</p>

Pathogenic role of glycan-specific IgG antibodies in IgA nephropathy.

BACKGROUND: Accumulating evidences proved the important roles of circulating IgA1-containing immune complexes (cIgA1) in IgA nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG antibody have been identified as major components in cIgA1. Before, Gd-IgA1 was reported as a vital factor in IgAN, partly via of its pathogenic role to induce mesangial cells activation. However, we still lack direct evidences to clarify the biological effect of glycan-specific IgG antibody in IgAN. METHODS: In the present study, we enrolled 35 IgAN patients and 17 age- and sex-matched healthy controls. Using uniform aberrant glycosylated IgA1 molecules, and IgG from different individuals, we in vitro prepared IgG-ddIgA1 complexes, and compared the biological differences among these immune complexes regarding their proliferative and inflammatory effects on mesangial cells. RESULTS: IgG-ddIgA1 complexes from both patients with IgA nephropathy (IgAN-IgG-dd-IgA1) and healthy controls (HC-IgG-dd-IgA1) could induce the proliferation of mesangial cells and up-regulate expression of MCP-1, IL-6 and CXCL1. The levels of mesangial cells proliferation induced by IgAN-IgG-dd-IgA1 were significantly higher than those induced by HC-IgG-dd-IgA1 (1.10 ± 0.05 vs. 1.03 ± 0.03; p < 0.001). However, the levels of secreted MCP-1, IL-6 and CXCL1 from mesangial cells challenged by IgAN-IgG-dd-IgA1 and HC-IgG-dd-IgA1 were comparable. CONCLUSIONS: We found that glycan-specific IgG antibodies derived from patients with IgAN had the biological effect to induce mesangial cells proliferation. Moreover, in the present study we also established a method for in vitro preparation of pathogenic IgG-ddIgA1 complexes, which could be applied in future studies exploring IgAN pathogenesis.

Prognostic value of metabolic variables of [18F]FDG PET/CT in surgically resected stage I lung adenocarcinoma.

The objective of this study was to assess the prognostic value of metabolic tumor burden measured by positron emission tomography/computed tomography (PET/CT) in patients with stage I lung adenocarcinoma.We reviewed 127 consecutive patients with pathologically proven stage I lung adenocarcinoma who underwent pretreatment [18F]FDG PET/CT scans in our hospital from 2005 June to 2012 June. The maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and computed tomography volume (CTV) were measured. The Kaplan-Meier and Cox proportional hazards model were used with age, gender, TNM stage, clinical stage, histological grade, nodule type, tumor size, and metabolic parameters to predict progression-free survival (PFS). The cut-off point was determined through receiver-operating characteristic curve.In univariate analysis, the histological grade, nodule type, diameter (cut-off value of 2.0 cm), CTV (6.56 cm), SUVmax (3.25 g/mL), SUVmean (1.58 g/mL), SUVpeak (1.84 g/mL), MTV (4.80 cm), and TLG (10.40) were significantly associated with PFS (all P value < .05). Patients with poorly differentiated adenocarcinoma, solid nodule type, large size, and high metabolic tumor burden were associated with poor prognosis. In multivariate analysis, only histological grade was independent prognostic factors for progression with a P value of .005 (RR, 0.355; 95% CI, 0.173-0.728). Among 5 PET/CT metabolic parameters, only MTV was independent prognostic factors for progression with a P value of .031 (RR, 1.118; 95% CI, 1.010-1.237).Histological grade was an independent predictor for progression in patients with stage I lung adenocarcinoma. Among 5 PET/CT metabolic parameters, only MTV was an independent predictor for progression.

Diagnostic value of single-source dual-energy spectral computed tomography for papillary thyroid microcarcinomas.

BACKGROUND: Ultrasound (US) and computed tomography (CT) are common diagnostic imaging methods for detecting and diagnosing papillary thyroid microcarcinoma (PTMC). However, single-source dual-energy spectral computed tomography (spectral CT) reduces beam hardening artefacts and optimizes contrast, which may add value in detecting PTMC. OBJECTIVE: To investigate values of applying single-source dual-energy spectral CT for diagnosing PTMCs, in comparison with high frequency ultrasound and conventional polychromatic images. METHODS: Thirty-one patients with suspected PTMC underwent contrast-enhanced dual-energy spectral CT. The images were analyzed by two experienced radiologists. Noise and contrast-noise-ratio (CNR) were compared between conventional CT and spectral CT. Ultrasonography was also performed by an experienced radiologist with a 7 to 12-MHz linear array transducer. Detection and diagnostic sensitivity were determined and compared. RESULTS: Forty-six pathologically-confirmed PTMC lesions were detected in 31 patients. Spectral CT had lower noise and higher CNR than conventional CT (P < 0.05). US detected more tumors (45/46 [97.8%] than conventional CT images (40/46 [87.0%]) or spectral CT images (44/46 [95.7%]). Among them, 30 (65.2%), 36 (78.3%), and 40 (87.0%) lesions were diagnosed correctly by conventional CT, spectral CT and US, respectively. Spectral CT had higher sensitivity than conventional CT (P = 0.031). However, there was no significant difference between spectral CT and US diagnostic sensitivities (P = 0.125). CONCLUSION: Single-source dual-energy spectral CT was superior to conventional polychromatic images and similar to high frequency ultrasound in detecting and diagnosing for PTMCs. CT had advantages in detecting level VI and VII lymph nodes. Spectral CT and US provided good results for PTMC, and aid preoperative diagnosis.

Comparison of different automated lesion delineation methods for metabolic tumor volume of 18F-FDG PET/CT in patients with stage I lung adenocarcinoma.

The aim of the study was to investigate the suitable segmentation method in small, low uptake and heterogeneous nodules of stage I lung adenocarcinoma.133 stage I lung adenocarcinoma patients with F-FDG PET/CT scans were enrolled in this retrospective study. All lesions were divided into different groups according to nodule density, nodule size, and the maximum standard uptake value (SUVmax) level. Four different PET segmentation methods were performed, including percentage threshold of SUVmax (T42% and T42% × RC), gradient-based threshold (adaptive iterative algorithm, AT-AIA), and background-related threshold (adaptive thresholding at 40% SUVmax, AT40%) approaches. The MTVs were evaluated and compared with CT volume (CTV). Percentage volume error (%VE) compared to CTV was calculated and the correlations between MTVs and CTV were analyzed.AT-AIA had the highest accuracy in large, high uptake, and solid nodules (72.5%, 72.4%, and 65.6%, respectively). AT40% had the highest accuracy in small, low uptake and nonsolid nodules (56.6%, 56.1%, and 62.6%, respectively). In part-solid nodules, the accuracy of AT-AIA (60.0%) and AT40% (56.7%) were higher than that of T42% and T42% × RC. The MTV of AT-AIA was in excellent correlation with the CTV in solid nodules (R = 0.831, P < .001) and in high uptake nodules (R = 0.830, P < .001). The MTV of AT40% was in good correlation with the CTV in nonsolid nodules (R = 0.686, P = .003) and in part-solid nodules (R = 0.731, P < .001).AT40% showed best performance in small, low uptake, nonsolid and part-solid lesions. AT-AIA was suitable for large, high uptake, and solid lesions.

MicroRNA 182 inhibits CD4+CD25+Foxp3+ Treg differentiation in experimental autoimmune encephalomyelitis.

MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3+ T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3+ T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway.

Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA Nephropathy.

BACKGROUND AND OBJECTIVES: Proteinuria is an independent predictor for IgA nephropathy (IgAN) progression. Urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and 24-hour urine protein excretion (UPE) are widely used for proteinuria evaluation in clinical practice. Here, we evaluated the association of these measurements with clinical and histologic findings of IgAN and explored which was the best predictor of IgAN prognosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with IgAN were followed up for ≥12 months, were diagnosed between 2003 and 2012, and had urine samples available (438 patients). Spot urine ACR, protein-to-creatinine ratio, and 24-hour UPE at the time of renal biopsy were measured on a Hitachi Automatic Biochemical Analyzer 7180 (Hitachi, Yokohama, Japan). RESULTS: In our patients, ACR, protein-to-creatinine ratio, and 24-hour UPE were highly correlated (correlation coefficients: 0.71-0.87). They showed good relationships with acknowledged markers reflecting IgAN severity, including eGFR, hypertension, and the biopsy parameter (Oxford severity of tubular atrophy/interstitial fibrosis parameter). However, only ACR presented with positive association with the Oxford segmental glomerulosclerosis/adhesion parameter and extracapillary proliferation lesions. The follow-up time was 37.0 (22.0-58.0) months, with the last follow-up on April 18, 2014. In total, 124 patients reached the composite end point (30% eGFR decline, ESRD, or death). In univariate survival analysis, ACR consistently had better performance than protein-to-creatinine ratio and 24-hour UPE as represented by higher area under the curve using time-dependent survival analysis. When adjusted for well known risk factors for IgAN progression, ACR was most significantly associated with the composite end point (hazard ratio, 1.56 per 1-SD change of standard normalized square root-transformed ACR; 95% confidence interval, 1.29 to 1.89; P<0.001). Compared with protein-to-creatinine ratio and 24-hour UPE, addition of ACR to traditional risk factors resulted in more improvement in the predictive ability of IgAN progression (c statistic: ACR=0.70; protein-to-creatinine ratio =0.68; 24-hour UPE =0.69; Akaike information criterion: ACR=1217.85; protein-to-creatinine ratio =1229.28; 24-hour UPE =1234.96; P<0.001). CONCLUSIONS: In IgAN, ACR, protein-to-creatinine ratio, and 24-hour UPE had comparable association with severe clinical and histologic findings. Compared with protein-to-creatinine ratio and 24-hour UPE, ACR showed slightly better performance in predicting IgAN progression.

Prostate Cancer Detection with Multiparametric Magnetic Resonance Imaging: Prostate Imaging Reporting and Data System Version 1 versus Version 2 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate Imaging Reporting and Data System (PI-RADS) is a globally acceptable standardization for multiparametric magnetic resonance imaging (mp-MRI) in prostate cancer (PCa) diagnosis. The American College of Radiology revised the PI-RADS to address the limitations of version 1 in December 2014. This study aimed to determine whether the PI-RADS version 2 (PI-RADS v2) scoring system improves the diagnostic accuracy of mp-MRI of the prostate compared with PI-RADS v1.</p><p><b>METHODS</b>This retrospective study was approved by the institutional review board. A total of 401 consecutive patients, with clinically suspicious PCa undergoing 3.0 T mp-MRI (T2-weighted imaging + diffusion-weighted imaging + DCE) before transrectal ultrasound-guided biopsy between June 2013 and July 2015, were included in the study. All patients were scored using the 5-point PI-RADS scoring system based on either PI-RADS v1 or v2. Receiver operating characteristics were calculated for statistical analysis. Sensitivity, specificity, and diagnostic accuracy were compared using McNemar's test.</p><p><b>RESULTS</b>PCa was present in 150 of 401 (37.41%) patients. When we pooled data from both peripheral zone (PZ) and transition zone (TZ), the areas under the curve were 0.889 for PI-RADS v1 and 0.942 for v2 (P = 0.0001). Maximal accuracy was achieved with a score threshold of 4. At this threshold, in the PZ, similar sensitivity, specificity, and accuracy were achieved with v1 and v2 (all P > 0.05). In the TZ, sensitivity was higher for v2 than for v1 (96.36% vs. 76.36%, P = 0.003), specificity was similar for v2 and v1 (90.24% vs. 84.15%, P = 0.227), and accuracy was higher for v2 than for v1 (92.70% vs. 81.02%, P = 0.002).</p><p><b>CONCLUSIONS</b>Both v1 and v2 showed good diagnostic performance for the detection of PCa. However, in the TZ, the performance was better with v2 than with v1.</p>

CXCL1 Triggers Caspase-3 Dependent Tau Cleavage in Long-Term Neuronal Cultures and in the Hippocampus of Aged Mice: Implications in Alzheimer's Disease.

Truncation of tau protein is considered an early event in Alzheimer's disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons. The cleaved tau formed varicosities or bead-like structures along the neurites, an abnormal distribution of tau induced by CXCL1 that has not been observed previously. CXCL1-induced activation of GSK3ß and the subsequent phosphorylation of tau preceded and were required for caspase-3 activation and tau cleavage. Moreover, intrahippocampal microinjection of lentiviral CXCL1 induced tau cleavage in hippocampal neurons in aged (15-18 months of age) but not adult mice (5-10 months of age). Our data highlight a new role of CXCR2 in tau cleavage and suggest that targeting CXCR2 may offer therapeutic benefits to patients with AD and potentially other tauopathies.

Feasibility Study of Using Gemstone Spectral Imaging (GSI) and Adaptive Statistical Iterative Reconstruction (ASIR) for Reducing Radiation and Iodine Contrast Dose in Abdominal CT Patients with High BMI Values.

PURPOSE: To prospectively investigate the effect of using Gemstone Spectral Imaging (GSI) and adaptive statistical iterative reconstruction (ASIR) for reducing radiation and iodine contrast dose in abdominal CT patients with high BMI values. MATERIALS AND METHODS: 26 patients (weight > 65kg and BMI ≥ 22) underwent abdominal CT using GSI mode with 300mgI/kg contrast material as study group (group A). Another 21 patients (weight ≤ 65kg and BMI ≥ 22) were scanned with a conventional 120 kVp tube voltage for noise index (NI) of 11 with 450mgI/kg contrast material as control group (group B). GSI images were reconstructed at 60keV with 50%ASIR and the conventional 120kVp images were reconstructed with FBP reconstruction. The CT values, standard deviation (SD), signal-noise-ratio (SNR), contrast-noise-ratio (CNR) of 26 landmarks were quantitatively measured and image quality qualitatively assessed using statistical analysis. RESULTS: As for the quantitative analysis, the difference of CNR between groups A and B was all significant except for the mesenteric vein. The SNR in group A was higher than B except the mesenteric artery and splenic artery. As for the qualitative analysis, all images had diagnostic quality and the agreement for image quality assessment between the reviewers was substantial (kappa = 0.684). CT dose index (CTDI) values for non-enhanced, arterial phase and portal phase in group A were decreased by 49.04%, 40.51% and 40.54% compared with group B (P = 0.000), respectively. The total dose and the injection rate for the contrast material were reduced by 14.40% and 14.95% in A compared with B. CONCLUSION: The use of GSI and ASIR provides similar enhancement in vessels and image quality with reduced radiation dose and contrast dose, compared with the use of conventional scan protocol.

Human neutrophil peptide 1-3, a component of the neutrophil extracellular trap, as a potential biomarker of lupus nephritis.

OBJECTIVE: Human neutrophil peptides (HNP) were recently implicated in the neutrophil extracellular trap (NET) complex, the impaired degradation of which has been associated with lupus nephritis (LN). METHODS: Forty LN patients, 40 SLE patients without kidney injury, 63 immunoglobulin A nephropathy (IgAN) patients, 20 minimal change disease (MCD) patients and 33 healthy controls were included in the present study. LN, IgAN and MCD patients were diagnosed with renal biopsy. LN patients were followed for a median period of 5.5 years. Clinical and laboratory data at the time of renal biopsy and follow-up were collected for each LN patient. Serum levels of HNP1-3 were measured with enzyme-linked immunosorbent assay. RESULTS: Serum HNP1-3 levels in LN patients were significantly higher than for SLE patients without kidney injury (P < 0.001), IgAN patients (P = 0.012), MCD patients (P = 0.010) and healthy controls (P = 0.022). Serum HNP1-3 levels were an independent indicator of LN (P = 0.006, OR = 7.5, 95% CI, 1.782-31.842), were statistically correlated with urinary protein excretion (P = 0.009) and activity index (P = 0.042) and were only marginally correlated with neutrophils (P = 0.054) and white blood cell counts (P = 0.051). Serum levels of HNP1-3 were a predictor of proteinuria remission after correction for multiple parameters (multivariate hazard 0.209; 95% CI 0.046-0.951; P = 0.043). CONCLUSIONS: The data from this study indicated that HNP1-3, one component of the NET, is a potential biomarker for LN.

Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: a large case-control study and meta-analysis.

OBJECTIVES: Recent animal experiments showed that CCR5-deficient lupus mice (CCR5(-/-)) were closely associated with aggravated lupus nephritis. CCR5 Δ32 variation, a nonsynonymous mutation of CCR5, resulted in altered CCR5 function. However, the CCR5 Δ32 mutation in human lupus nephritis has been rarely reported in the literature. METHODS: A large case-control study that included 2010 samples from a Chinese population was conducted, followed by a meta-analysis combining the current and previously published studies to explore the effect of CCR5 Δ32 on lupus nephritis susceptibility. RESULTS: Four CCR5 Δ32 heterozygote carriers were detected in lupus nephritis patients only. We detected no CCR5 Δ32 homozygotes in our study population. In the meta-analysis, including 1,092 cases and 2,229 controls, we found great heterogeneity between studies (p < 0.001, I(2)( )= 89.6%). Furthermore, stratified and sensitivity analyses suggested that ethnicity and CCR5 Δ32 allele frequency were the main origin of heterogeneity. In the subgroups without obvious heterogeneity, we observed a positive correlation between CCR5 Δ32 and lupus nephritis risk (p < 0.05). CONCLUSIONS: Our study confirmed that the CCR5 Δ32 mutation is a very rare variation found in the Chinese population with Han ethnicity. However, CCR5 Δ32 might play a role in lupus nephritis susceptibility. Future replications and functional studies are needed.

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort. PATIENTS AND METHODS: 60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese. RESULTS: Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.74*10(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p = 2.28*10(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65×10(-2)) as well as gross hematuria (p = 4.53×10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67×10(-2)) as well as eGFR (p = 5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions. CONCLUSION: Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.

Alpha-defensin DEFA1A3 gene copy number variation in Asians and its genetic association study in Chinese systemic lupus erythematosus patients.

Neutrophil extracellular traps (NETs) were closely associated with activation of type I interferon (IFN) pathway in systemic lupus erythematosus (SLE). We aimed to study the genetic basis of NETs-DEFA1A3 copy number variations (CNV) in SLE and HapMap CHB+JPT populations by quantitative real-time PCR and whole genome sequences data. DEFA1A3 CNs did not differ significantly between SLE patients and controls. DEFA1A3 CNs ranged from 3 to 11 in CHB and 4 to 16 in JPT. The median of DEFA1A3 CNV of CHB (6 copies) was significantly lower than that of JPT (9 copies). Associations of genotype of tag SNP rs2738113 with DEFA1A3 CNs and mRNA expression of IFNα were observed in CHB and JPT populations. Our data provided a genetic reference of DEFA1A3 CNV for further studies and suggested that the genetic pathogenesis of NETs, as well as DEFA1A3 in SLE should be further evaluated, specially in different populations.