XGBoost-based multiparameters from dual-energy computed tomography for the differentiation of multiple myeloma of the spine from vertebral osteolytic metastases.

OBJECTIVES: To evaluate the performance of extreme gradient boosting (XGBoost) combined with multiparameters from dual-energy computed tomography (mpDECT) to differentiate between multiple myeloma (MM) of the spine and vertebral osteolytic metastases (VOM). METHODS: For this retrospective study, 28 patients (83 lesions) with MM of the spine and 23 patients (54 lesions) with VOM who underwent DECT were included. The mpDECT for each lesion, including normalized effective atomic number, slope of the spectral Hounsfield unit curve, CT attenuation, and virtual noncalcium (VNCa), was obtained. Boruta was used to select the key parameters, and then subsequently merged with XGBoost to yield a prediction model. The lesions were divided into the training and testing group in a 3:1 ratio. The highest performance of the univariate analysis was compared with XGBoost using the Delong test. RESULTS: The mpDECT of MM was significantly lower than that of VOM (all p < 0.05). In univariate analysis, VNCa had the highest area under the receiver operating characteristic curve (AUC) in the training group (0.81) and testing group (0.87). Based on Boruta, 6 parameters of DECT were selected for XGBoost model construction. The XGBoost model achieved an excellent and stable diagnostic performance, as shown in the training group (AUC of 1.0) and testing group (AUC of 0.97), with a sensitivity of 80%, a specificity of 95%, and an accuracy of 88%, which was superior to VNCa (p < 0.05). CONCLUSIONS: XGBoost combined with mpDECT yielded promising performance in differentiating between MM of the spine and VOM. KEY POINTS: • The multiparameters obtained from dual-energy CT of multiple myeloma differed significantly from those of vertebral osteolytic metastases. • The virtual noncalcium offered the highest AUC in the univariate analysis to distinguish multiple myeloma from vertebral osteolytic metastases. • Extreme gradient boosting combined with multiparameters from dual-energy CT had a promising performance to distinguish multiple myeloma from vertebral osteolytic metastases.

Cystatin C and eGFRCKD-EPI-CysC: novel biomarkers for renal impairment diagnosis and two-year progression-free survival in multiple myeloma.

To evaluate cystatin C (CysC) and estimation of glomerular filtration rate (GFR) calculated using the formula, CKD-EPI-CysC (eGFRCKD-EPI-CysC) for renal impairment diagnosis and predicting the prognosis of patients with multiple myeloma (MM). One hundred-fourteen patients with MM and 38 healthy individuals were recruited for the study. Data on clinical characteristics and renal function-related biochemical indicators were collected and analyzed. Patients with MM had increased levels of CysC (1.25 (0.97-2.31) vs. 0.84 (0.80-0.92), respectively, p < 0.001) and decreased levels of eGFRCKD-EPI-CysC (53.0 (24.4-81.1) vs. 97.2 (87.0-104.5), respectively, p < 0.001), compared with healthy individuals. There were significantly more patients with elevated CysC levels than with elevated sCr levels (64.9% vs. 41.2%, respectively, p < 0.001). The CKD-EPI-CysC formula detected more patients with eGFR < 60 ml/(min × 1.73 m2) than the CKD-EPI-sCr formula (52.63% vs. 37.72%, respectively, p < 0.001). Correlation analysis found that only CysC, eGFRCKD-EPI-CysC, and eGFRCKD-EPI-sCr-CysC strongly correlated with ß2-microglobulin in group ISS-I. Logistic regression analysis was used to screen CysC (OR = 1.495, 95% CI = 1.097-2.038, p = 0.011) and eGFRCKD-EPI-CysC (OR = 0.980, 95% CI = 0.967-0.993, p = 0.003) as independent prognostic indicators for 2-year-progression-free survival (PFS) of patients with MM. Receiver operating characteristic curve analysis found that CysC values >1.70 mg/L had 67.6% sensitivity and 65.2% specificity and eGFRCKD-EPI-CysC values <38.62 ml/(min × 1.73 m2) had 65.2% sensitivity and 67.6% specificity for 2-year PFS of patients with MM. In summary, CysC and eGFRCKD-EPI-CysC were more sensitive than sCr and eGFRCKD-EPI-sCr for predicting renal impairment in patients newly diagnosed with MM. Increased CysC and decreased eGFRCKD-EPI-CysC levels were effective predictors of 2-year PFS of patients with MM.

Initial Investigation of Clinical Value of Noise-Optimized Virtual Monoenergetic Images Derived From Dual-Energy Computed Tomography Angiography in Preoperative Perforator Planning of Anterolateral Thigh Flap Transplantation.

OBJECTIVE: To objectively and subjectively assess the image characteristics of noise-optimized virtual monoenergetic images [MEI (+)] and polyenergetic images (PEIs) from dual-energy computed tomography angiography and then to explore the clinical value of the optimal MEI (+) in preoperative perforator planning of anterolateral thigh (ALT) flap transplantation. METHODS: Sixteen patients (32 thighs) who underwent lower extremity run-off dual-energy computed tomography angiography for planning ALT flap transplantation were enrolled. One standard PEI and 5 MEI (+) in 10-keV intervals (range, 40-80 keV) were reconstructed. First, we compared the image quality subjectively (branch order, image quality, and vascular network continuity) and objectively (vascular attenuation, image noise, signal-to-noise ratio, and the contrast-to-noise ratio). Then, we compared the clinical value (number, type, source artery, pedicle length, caliber, and location of all sizable perforators) between the optimal MEI (+) and PEI groups. RESULTS: The 40-keV MEI (+) was rated superior subjective and objective image quality metrics to PEI (all P < 0.001). Compared with PEI, 40 keV MEI (+) increased the number of visible perforators, the percentage of perforators with identifiable types, and the measurable length of perforator pedicle (all P < 0.001). CONCLUSIONS: We recommend 40 keV MEI (+) for the visualization of perforators and their contribution to the selection and location of suitable perforators in preoperative planning for ALT flaps.

Evaluating the Image Quality of Monoenergetic Images From Dual-Energy Computed Tomography With Low-Concentration and Low-Flow-Rate Contrast Media for the Arterials Supply to the Nipple-Areola Complex in Breast Cancer Compared With Conventional Computed Tomography Angiography.

OBJECTIVE: The objective of this study was to evaluate the image quality of monoenergetic images (MEIs (+)) acquired from dual-energy computed tomography with low-concentration and low-flow-rate contrast media for the arterial supply to the nipple-areola complex (NAC) in breast cancer compared with conventional computed tomography angiography (CTA). METHODS: We enrolled 25 patients (MEI (+)300 group, 300 mg/mL and 2.5 mL/s of contrast media) and 23 patients (CTA370 group, 370 mg/mL and 3.5 mL/s of contrast media) for assessing NAC blood supply angiography. The image quality of the 2 groups was evaluated objectively and subjectively. RESULTS: The 40 keV MEI (+)300 demonstrated higher attenuation and contrast-to-noise ratio than CTA370 group (P < 0.001). The subjective image quality and visualization of the arteries were comparable between 2 groups. CONCLUSIONS: The 40 keV MEI (+)300 acquired from dual-energy computed tomography can achieve comparable image quality of arterial supply to NAC with low-concentration and low-flow-rate contrast media in breast cancer compared with CTA370.

Autoantibodies to chromogranin A are potential diagnostic biomarkers for non-small cell lung cancer.

Cancer-associated autoantibodies show promise as sensitive biomarkers for the early detection of cancer. To test the immunogenicity of chromogranin A (ChgA) as a B cell autoantigen and to assess the potential applications of ChgA autoantibodies as novel biomarkers for the diagnosis of non-small cell lung cancer (NSCLC), we developed a high-content peptide microarray using ChgA peptides. Autoantibody profiling was carried out using sera from 168 individuals with NSCLC and 97 healthy controls. We present evidence for the occurrence of autoantibodies to ChgA peptides in patient sera and identified five highly responsive peptides in the NSCLC group using significance analysis of microarray (SAM). Receiver operating characteristic analyses showed that ChgA autoantibodies are valuable in the predictive diagnosis of NSCLC, suggesting that serum autoantibodies to ChgA-derived peptides are promising novel markers of NSCLC. Moreover, the high-content peptide microarray antibody profiling reported in this work provides a powerful tool to visualize the overall B cell response to ChgA peptides and should enable the rapid development of in-depth research into ChgA.

Predicting histopathological types and molecular subtype of breast tumors: A comparative study using amide proton transfer-weighted imaging, intravoxel incoherent motion and diffusion kurtosis imaging.

PURPOSE: To evaluate the predictive performance of multiparameter and histogram features derived from amide proton transfer-weighted imaging (APTWI), intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) for histopathological types of breast tumors. METHODS: Region of interest (ROI) was delineated by outlining the largest slice of the tumor on the false-color images of the DKI, IVIM and APTWI parameters, and extracted the histogram features. Receiver operating characteristic (ROC) curve was used to evaluate the performance of parameters in predicting benign and malignant breast lesions, molecular prognostic biomarkers, lymph node status, and subtypes of breast lesions. The Spearman correlation coefficient was used to determine the correlations between each parameter and clinical-pathological factors. RESULTS: All 52 breast lesions were enrolled in this prospective study, including 8 benign lesions and 44 breast cancers. To diagnose malignant and benign breast lesions, the value of APT (min) performed best, with the AUC reaching 0.983. According to the different imaging methods, the APTWI performed best. To predict the positive status of ER, PR, Ki67, the value of Dapp (uniformity), Dapp (uniformity), f (entropy) performed best, with the AUC values reaching 0.743, 0.770, 0.848, respectively. For the identification of Luminal B, HER2-enriched, and TNBC breast cancers, Kapp (max), f (kurtosis), and Dapp (uniformity) performed best, with AUC values reaching 0.679, 0.826, 0.771, respectively. CONCLUSION: This study found the APTWI, IVIM and DKI parameters could diagnose breast cancer. The histogram features of DKI and IVIM, based on tumor heterogeneity, may help to predict breast cancer subtypes.

Evaluation of optimal monoenergetic images acquired by dual-energy CT in the diagnosis of T staging of thoracic esophageal cancer.

OBJECTIVES: The purpose of our study was to objectively and subjectively assess optimal monoenergetic image (MEI (+)) characteristics from dual-energy CT (DECT) and the diagnostic performance for the T staging in patients with thoracic esophageal cancer (EC). METHODS: In this retrospective study, patients with histopathologically confirmed EC who underwent DECT from September 2019 to December 2020 were enrolled. One standard polyenergetic image (PEI) and five MEI (+) were reconstructed. Two readers independently assessed the lesion conspicuity subjectively and calculated the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) of EC. Two readers independently assessed the T stage on the optimal MEI (+) and PEI subjectively. Multiple quantitative parameters were measured to assess the diagnostic performance to identify T1-2 from T3-4 in EC patients. RESULTS: The study included 68 patients. Subjectively, primary tumor delineation received the highest ratings in MEI (+) 40 keV of the venous phase. Objectively, MEI (+) images showed significantly higher SNR compared with PEI (p < 0.05), peaking at MEI (+) 40 keV in the venous phase. CNR of tumor (MEI (+) 40 keV -80 keV) was all significantly higher than PEI in arterial and venous phases (p < 0.05), peaking at MEI (+) 40 keV in venous phases. The agreement between MEI (+) 40 keV and pathologic T categories was 81.63% (40/49). Rho values in venous phases had excellent diagnostic efficiency for identifying T1-2 from T3-4 (AUC = 0.84). CONCLUSIONS: MEI (+) reconstructions at low keV in the venous phase improved the assessment of lesion conspicuity and also have great potential for preoperative assessment of T staging in patients with EC.

Multiple parameters from ultrafast dynamic contrast-enhanced magnetic resonance imaging to discriminate between benign and malignant breast lesions: Comparison with apparent diffusion coefficient.

PURPOSE: The purpose of this study was first to assess the diagnostic performance of ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters compared to apparent diffusion coefficient (ADC) for distinguishing benign from malignant breast lesions and second to investigate the complementarity of ultrafast DCE-MRI with DWI in that task. MATERIALS AND METHODS: A total of 142 women (mean age, 48.42 ± 11.03 [SD]) years; range: 14-78 years) with 150 breast lesions who underwent breast ultrafast DCE-MRI were prospectively recruited. Ultrafast DCE-MRI semi-quantitative parameters (maximum slope [MS], time to peak [TTP], time to enhancement [TTE], and initial area under curve in 60 s [iAUC]), ultrafast DCE-MRI quantitative parameters (Kep, Ktrans, and Ve), and the ADC were estimated and compared between benign and malignant breast lesions. Classification performances were assessed using area under the receiver operating characteristic curve (AUC) and compared using Delong test. RESULTS: The ultrafast DCE-MRI semi-quantitative multiparameters (AUC, 0.913; 95% CI: 0.856-0.953) showed better classification performance than the quantitative multiparameters (AUC, 0.818; 95% CI: 0.747-0.876) (P = 0.022). No differences in AUC were found between ultrafast DCE-MRI semi-quantitative multiparameters and ADC (AUC, 0.912; 95% CI: 0.855-0.952) (P = 0.990). The combination of ultrafast DCE-MRI semi-quantitative multiparameters and ADC (AUC, 0.960; 95% CI: 0.915-0.985) showed better classification performance than the ultrafast DCE-MRI semi-quantitative multiparameters (P = 0.014) and quantitative multiparameters (P < 0.001). CONCLUSION: Ultrafast DCE-MRI can be used as an accurate method for discriminating benign from malignant breast lesions. The combination of ultrafast DCE-MRI and DWI significantly increases the diagnostic value of ultrafast DCE-MRI.

Early prediction of pathologic complete response of breast cancer after neoadjuvant chemotherapy using longitudinal ultrafast dynamic contrast-enhanced MRI.

PURPOSE: The purpose of this study was to evaluate the temporal trends of ultrafast dynamic contrast-enhanced (DCE)-MRI during neoadjuvant chemotherapy (NAC) and to investigate whether the changes in DCE-MRI parameters could early predict pathologic complete response (pCR) of breast cancer. MATERIALS AND METHODS: This longitudinal study prospectively recruited consecutive participants with breast cancer who underwent ultrafast DCE-MRI examinations before treatment and after two, four, and six NAC cycles between February 2021 and February 2022. Five ultrafast DCE-MRI parameters (maximum slope [MS], time-to-peak [TTP], time-to-enhancement [TTE], peak enhancement intensity [PEI], and initial area under the curve in 60 s [iAUC]) and tumor size were measured at each timepoint. The changes in parameters between each pair of adjacent timepoints were additionally measured and compared between the pCR and non-pCR groups. Longitudinal data were analyzed using generalized estimating equations. The performance for predicting pCR was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Sixty-seven women (mean age, 50 ± 8 [standard deviation] years; age range: 25-69 years) were included, 19 of whom achieved pCR. MS, PEI, iAUC, and tumor size decreased, while TTP increased during NAC (all P < 0.001). The AUC (0.92; 95% confidence interval [CI]: 0.83-0.97) of the model incorporating ultrafast DCE-MRI parameter change values (from timepoints 1 to 2) and clinicopathologic characteristics was greater than that of the clinical model (AUC, 0.79; 95% CI: 0.68-0.88) and ultrafast DCE-MRI parameter model at timepoint 2 when combined with clinicopathologic characteristics (AUC, 0.82; 95% CI: 0.71-0.90) (P = 0.01 and 0.02). CONCLUSION: Early changes in ultrafast DCE-MRI parameters after NAC combined with clinicopathologic characteristics could serve as predictive markers of pCR of breast cancer.

Analysis of Serum IgG1 to Predict Progression and Therapeutic Effect in Patients with Multiple Myeloma.

Objective: The correlation between laboratory indicators and clinical treatment effects and the prognosis of multiple myeloma remains poorly understood. Therefore, our study investigated whether serum IgG subclasses could be employed as potential indicators contributed to evaluate the therapeutic effect and prognosis of patients with multiple myeloma. Patients and Methods. Records of patients with multiple myeloma were initially diagnosed at the First Affiliated Hospital of Soochow University, China, from August 1, 2017, to February 28, 2020. The assessment abilities of serological indicators for therapeutic effect were evaluated in patients compared with healthy controls. Results: In 560 study patients with multiple myeloma, serum IgA, IgG, IgM, κ-LC, and λ-LC increased by15%, 33.04%, 1.96%, 27.50%, and 26.43%, respectively. Further analysis found that IgG1, IgG2, IgG3, and IgG4 were over the upper limit of the reference range with 26.38%, 6.09%, 8.12%, and 4.64%, respectively. κ-LC and λ-LC were found in the urine in 65.13% and 29.70%, respectively. In peripheral blood, the proportion of CD3+CD4+, CD3-CD19+ cells, and CD4+/CD8+ decreased, whereas CD3+CD8+ cells and CD16+/CD56+ increased, and the associated cytokines IL-2, IL-4, IL-6, TNF-α, and IFN-γ were upregulated in patients when compared with healthy controls. Furthermore, the serum levels of IgA, IgG, IgG1, IgG2, IgG3, and IgG4 gradually decreased in patients before, during, and after treatment. Similar results were found in serum and urine κ-LC and λ-LC. Conclusion: Serum IgG1 level could serve as the potential indicator for evaluating the therapeutic effect for patients with multiple myeloma. κ-LC and λ-LC also have the potential to be prognostic indicators. More studies are warranted to explore these serological indicators for personalized therapy in the future.

Application of machine learning with multiparametric dual-energy computed tomography of the breast to differentiate between benign and malignant lesions.

BACKGROUND: Multiparametric dual-energy computed tomography (mpDECT) is widely used to differentiate various kinds of tumors; however, the data regarding its diagnostic performance with machine learning to diagnose breast tumors is limited. We evaluated univariate analysis and machine learning performance with mpDECT to distinguish between benign and malignant breast lesions. METHODS: In total, 172 patients with 214 breast lesions (55 benign and 159 malignant) who underwent preoperative dual-phase contrast-enhanced DECT were included in this retrospective study. Twelve quantitative features were extracted for each lesion, including CT attenuation (precontrast, arterial, and venous phases), the arterial-venous phase difference in normalized effective atomic number (nZeff), normalized iodine concentration (NIC), and slope of the spectral Hounsfield unit (HU) curve (λHu). Predictive models were developed using univariate analysis and eight machine learning methods [logistic regression, extreme gradient boosting (XGBoost), stochastic gradient descent (SGD), linear discriminant analysis (LDA), adaptive boosting (AdaBoost), random forest (RF), decision tree, and linear support vector machine (SVM)]. Classification performances were assessed based on the area under the receiver operating characteristic curve (AUROC). The best performances of the conventional univariate analysis and machine learning methods were compared using the Delong test. RESULTS: The univariate analysis showed that the venous phase λHu had the highest AUROC (0.88). Machine learning with mpDECT achieved an excellent and stable diagnostic performance, as shown by the mean classification performances in the training dataset (AUROC, 0.88-0.99) and testing (AUROC, 0.83-0.96) datasets. The performance of the AdaBoost model based on mpDECT was more stable than the other machine learning models and superior to the univariate analysis (AUROC, 0.96 vs. 0.88; P<0.001). CONCLUSIONS: The performance of the AdaBoost classifier based on mpDECT data achieved the highest mean accuracy compared to the other machine learning models and univariate analysis in differentiating between benign and malignant breast lesions.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model.

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

Clinical Value of Pepsinogen in the Screening, Prevention, and Diagnosis of Gastric Cancer.

OBJECTIVES: To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. METHODS: The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. RESULTS: Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003). CONCLUSIONS: The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.

Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum.

Expression of membrane CD276 (mB7-H3) has been reported on dendritic cells (DCs), monocytes, activated T cells, and various carcinoma cells. However, reports concerning its in vivo function have been inconsistent. Moreover, whether there is a soluble form of this protein is not known. In this study, using a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of B7-H3 (sB7-H3), we demonstrated the release of sB7-H3 by monocytes, DCs, activated T cells, and various mB7-H3+ but not mB7-H3- carcinoma cells. Release from cells was blocked by addition of a matrix metalloproteinase inhibitor (MMPI), which concomitantly caused the accumulation of B7-H3 on the cell surface. To determine the level of circulating sB7-H3, more than 200 serum samples were included in the study. The results indicated that sB7-H3 was present at high levels in all serum samples. Western blotting of sB7-H3 from cell culture supernatants or sera of healthy donors indicated that the molecular size was approximately 16 kDa. Soluble B7-H3 was able to bind to the B7-H3 receptor (B7-H3R) on activated T cells, which showed that sB7-H3 is a functionally active form. These results indicate that release of sB7-H3 from the cell surface is mediated by a matrix metalloproteinase and probably regulates B7-H3R/B7-H3 interactions in vivo. Cleavage of sB7-H3 to an active soluble form would alter both proximal and distal cellular responses.

CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

Molecular Characterization and Resistant Spectrum of Enterococci Isolated from a Haematology Unit in China.

OBJECTIVES: The present study screened clinical isolates of E. faecalis and E. faecium to determine resistant spectrum and the potential virulence genes characterization among them of haematology patients. METHODS: Clinical Enterococci isolates were obtained from a haematology unit in a tertiary care hospital in China. RESULTS: Among 125 isolates available for the investigation, 46 were identified as E. faecium, and 79 were E. faecalis. Urine was the most common source (82, 65.6%). E. faecium isolates were more resistant than E. faecalis. Among E. faecium, maximum resistance was seen against PEN 93.5% and AMP 93.5% followed by CIP 87%. Eight vancomycin-resistant E. faecium (VREfm) isolates were obtained, positive for vanA genotype. Of 125 Enterococci isolates, 67(53.6%) were acm, and 42.4%, 25.6%, 25.6%, 24.8%, 23.2%, 20.8%, 10.4% and 7.2% of isolates were positive for esp, cylL-A, asa 1, cylL-S, cpd, cylL-L, gel-E and ace, respectively. E. faecalis isolates have more virulence genes (VGs) than E. faecium. MLST analysis of VREfm identified three different STs (ST17, ST78 and ST203). CONCLUSION: The study provides the molecular characterization and resistant spectrum of Enterococci isolated from a haematology unit in China. Molecular analysis showed that all VREfm isolates belonged to pandemic clonal complex-17(CC17), associated with hospital-related isolates. Therefore, determining resistant spectrum and virulence characterization is crucial for the prevention and control of the spread of nosocomial infections caused by Enterococci in the haematology unit.

Phylogenetic Distribution of Virulence Genes Among ESBL-producing Uropathogenic Escherichia coli Isolated from Long-term Hospitalized Patients.

OBJECTIVES: The present study was aimed to investigate the antibiotic resistance, virulence potential and phylogenetic grouping of ESBL-producing uropathogenic Escherichia coli (EP-UPEC) isolated from long-term hospitalized patients. MATERIALS AND METHODS: EP-UPEC isolates from September 2013 to June 2014 at a tertiary care hospital of China were screened for ESBL-production by the double disk diffusion test. Isolates with ESBL-phenotype were further characterized by antibiotic resistance testing, PCR of different ESBL and virulence genes, and phylogenetic grouping. RESULTS: One hundred and twenty EP-UPEC were isolated from long-term hospitalized patients. All EP-UPEC isolates were resistant to Ampicillin, Cefazolin, Cefuroxime, Cefotaxime, Cefoperazone and Ceftriaxone, and the majority of EP-UPEC isolates were resistant to Piperacillin (82.5%), Ciprofloxacin (81.2%), Trimethoprim-Sulfamethoxazole (72.5%). The isolates showed the highest sensitivity against Imipenem (98.4%), Piperacillin/tazobactam (96.7%), Cefoperazone/sulbactam (91.7%), Amikacin (90.8%) and Cefepime (75.8%). Nine different ESBL genotype patterns were observed and CTX-M type was the most prevalent ESBL genotype (42.5%, 51/120). Majority of EP-UPEC isolates possess more than one ESBL genes. EP-UPEC isolates belonged mainly to phylogenetic group B2(36.7%) and D(35.0%). The prevalence of traT, ompT, iss, PAI, afa, fimH and papC were 75.8%, 63.3%, 63.3%, 60.8%, 40.8%, 19.2% and 6.7%, respectively. The number of virulence genes (VGs) detected was significantly higher in group B2 than in group A (ANOVA, p<0.001), group B1(ANOVA, p= 0.012) and D (ANOVA, p<0.001). CONCLUSIONS: EP-UPEC strains showed multidrug resistance and co-resistance to other non ß-lactam antibiotics. CTX-M was the most prevalent ESBL genotype and majority of EP-UPEC strains more than one ESBL genes. EP-UPEC strains belonged mainly to phylogenetic group B2 and D, and most of the virulence genes were more prevalent in group B2.

Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in dog plasma and its application to their pharmacokinetic study after oral administration of tripterygium glycosides tablets.

A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days.

Prevalence of Enterotoxin Genes and spa Genotypes of Methicillin-resistant Staphylococcus aureus from a Tertiary Care Hospital in China.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes a variety of infections. MRSA has evolved resistance to multiple antibiotics. Genetic background and virulence differs in different geographic regions. The present study was aimed to investigate the prevalence of enterotoxin genes and spa genotypes of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) isolated from a tertiary care hospital of Jiangsu province, China. MATERIALS AND METHODS: HA-MRSA isolates from August 2013 to April 2014 at a tertiary care hospital of China were collected. We investigated antimicrobial pattern, spa types, SCCmec types and the presence of 14 virulence genes. RESULTS: Eighty HA-MRSA isolates were collected. Results from SCCmec typing revealed that 73.8% were type II; 13.8% were type III; 12.5% were type V. There were 19 different spa types. Spa type t2460 was the most common (35.0%), followed by t002 (11.3%). CC5 was the predominant MLST CCs type (50%). The most frequent toxin genes were sea, seb, sed, sel, sen and seo (100.0%). None of the investigated isolates carried the sec or tst. CONCLUSION: Genotypic and virulence evaluation of the isolated HA-MRSA revealed that the isolates with CC5 and SCCmec II were the predominant type and highly homological. The virulence profiles mainly existed in the genes of sea, seb, sed, sel, sen, seo and ser. The prevalence of t2460 was an outbreak and the predominant spa type.

Expression levels of CD28, CTLA-4, PD-1 and Tim-3 as novel indicators of T-cell immune function in patients with chronic hepatitis B virus infection.

Chronic hepatitis B (CHB) is one of the most common types of infectious diseases worldwide. The interaction between hepatitis B virus (HBV) and the host immune response is vital for the clinical outcome of HBV infection. Costimulatory signals are key factors for the host immune response and play a critical role in innate immunity, particularly antiviral immunity. The aim of the present study was to investigate the correlation between the expression levels of costimulatory molecules and the different states of CHB infection, including the expression levels prior to and following treatment with antiviral agents. The expression levels of CD28, CTLA-4, PD-1, Tim-3 and T-cell subsets were determined by flow cytometry. The load of HBV DNA in the serum was detected by quantitative polymerase chain reaction and the serology markers, including HBeAg and alanine aminotransferase (ALT), were measured by conventional methods. Compared to the healthy control group, the expression levels of CD28 and CTLA-4 on CD4 T cells prior to and following treatment with antiviral agents (the pre- and post-treatment groups, respectively) were significantly decreased, while the expression levels of Tim-3 on CD4 and CD8 T cells were significantly increased. In addition, the expression levels of PD-1 on CD4 and CD8 T cells in the pre-treatment group were significantly increased compared to those in the post-treatment and healthy control groups. Moreover, the multivariate analysis revealed that the levels of ALT and HBV-DNA in the serum were significantly positively correlated with PD-1 expression levels. In conclusion, the expression levels of these costimulatory molecules reflect the immune dysfunction of T cells in patients with CHB and, combined with T-cell subset analysis may be used as a novel evaluation system of immune function in patients with HBV infection.