OBJECTIVES:Whether hemostatic status was correlated with the diverse types of acute kidney injury in cirrhotic patients is unclear. The present study aimed to investigate the relationship between hemostatic markers and the diverse types of acute kidney injury (AKI) in liver cirrhosis.PATIENTS AND METHODS:Cirrhotic patients with consecutive treatment at the First Affiliated Hospital of Medicine School, Zhejiang University, were pooled in a cohort. Their demographic and clinical data, biochemistry parameters and hemostatic markers were assessed to identify risk factors for the development and prognosis of AKI.RESULTS:A total of 773 cirrhotic patients were included in this cohort. Patients with hepatorenal syndrome (HRS) had significantly higher D-Dimer than those with the other types of AKI. In univariate COX regression, APTT, TT, INR, D-Dimer and Fib were correlated with the development of AKI, HRS and acute tubular necrosis (ATN), however, only D-Dimer remained independently associated with the development of AKI and HRS in multivariate COX regression. The area under the ROC curve of D-Dimer was 0.755 (95%CI, 0.718-0.793) in predicting the development of AKI, 0.879 (95%CI, 0.791-0.967) in predicting the development of HRS, respectively. D-Dimer was used for diagnosis of HRS with a sensitivity of 87.3% and specificity of 72.9% at the cutoff of 3.7 (mg/L FEU). Survival rates differed significantly between groups by D-Dimer level.CONCLUSIONS:Hemostatic markers were significantly associated with the diverse types of AKI. D-Dimer was an independent risk factor for HRS and correlated with a poor outcome in cirrhotic patients.

Since TGF-β was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-β in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-β is the principal regulator of the immune system, as deprivation of TGF-β signaling completely abrogates adaptive immunity. However, enhancing TGF-β signaling constrains the immune response through multiple mechanisms, including boosting Treg cell differentiation and inducing CD8+ T-cell apoptosis in the disease context. The love-hate relationship between TGF-β signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-β, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-β inhibition and immunotherapy have provide insights into the development of TGF-β-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-β and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-β signaling pathways as an emerging area of cancer therapy.

In vitro differentiation or expansion of stem and progenitor cells under chemical stimulation or genetic manipulation is used for understanding the molecular mechanisms of cell differentiation and self-renewal. However, concerns around the cell identity of in vitro –cultured cells exist. Bioinformatics methods, which rely heavily on signatures of cell types, have been developed to estimate cell types in bulk samples. The Tabula Muris Senis project provides an important basis for the comprehensive identification of signatures for different cell types. Here, we identified 46 cell type–specific (CTS) gene clusters for 83 mouse cell types. We conducted Gene Ontology term enrichment analysis on the gene clusters and revealed the specific functions of the relevant cell types. Next, we proposed a simple method, named CTSFinder, to identify different cell types between bulk RNA-Seq samples using the 46 CTS gene clusters. We applied CTSFinder on bulk RNA-Seq data from 17 organs and from developing mouse liver over different stages. We successfully identified the specific cell types between organs and captured the dynamics of different cell types during liver development. We applied CTSFinder with bulk RNA-Seq data from a growth factor–induced neural progenitor cell culture system and identified the dynamics of brain immune cells and nonimmune cells during the long-time cell culture. We also applied CTSFinder with bulk RNA-Seq data from reprogramming induced pluripotent stem cells and identified the stage when those cells were massively induced. Finally, we applied CTSFinder with bulk RNA-Seq data from in vivo and in vitro developing mouse retina and captured the dynamics of different cell types in the two development systems. The CTS gene clusters and CTSFinder method could thus serve as promising toolkits for assessing the cell identity of in vitro culture systems.

Background: The antiviral immune response is the main cause of hepatocyte damage and inflammatory necrosis. The serum free light chain, reflecting the immune function of B-cells, is strongly associated with inflammation and disease activity. We aimed to investigate the association of serum free light chain with the progression of chronic hepatitis B. Methods: A total of 208 eligible chronic hepatitis B patients who had undergone a liver biopsy were studied. Serum free light chains of all patients were measured by turbidimetry using an immunoassay. Liver histology was assessed according to the METAVIR scoring system (which grades the stage of fibrosis on a five-point scale, F0 = no fibrosis to F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity to A3 = severe activity). The association of serum free light chains with histological activity and fibrosis progression was evaluated. Results: The concentration of serum free light chains in CHB patients increased gradually with histological activity and fibrosis progression. The intensity of histological activity was significantly correlated with the serum free kappa chain (r = 0.658, P < 0.001) and the serum free lambda chain (0.675, P < 0.001). The stages of fibrosis were correlated with the serum free kappa chain (r = 0.683, P < 0.001) and serum free lambda chain (0.664, P < 0.001). After adjusting for age, sex and other synergic factors, the serum free kappa chain remained a potential risk factor, but the serum free lambda chain was no longer associated with liver cirrhosis. Similar to FIB-4 and RPR, the serum free kappa chain exhibited excellent performance in the prediction of liver cirrhosis. The AUCs of serum free Kappa chain, FIB-4 and RPR were 0.873, 0.880 and 0.895, respectively, which were significantly higher than those of the AAR and APRI (0.718 and 0.746). Conclusion: Our work revealed that serum free light chains were associated with histological activity and cirrhosis in chronic hepatitis B, which could play a crucial role in the immunopathogenesis of HBV-associated cirrhosis. In addition, free kappa light chain could be a useful predictor of liver cirrhosis.

The Yangshan Deep-Water Harbor (YDH) consists of a northern island chain and a southern island chain, with a deep channel between these two chains. It is frequently impacted by storm tides and waves caused by typhoons. The impacts of the interaction of tide, wave, and wind on storm surges in the channel-island system of the YDH were examined, using field data and a wave-current coupled numerical model, during the super typhoon Chan-hom. Field data showed that the tidal amplitude and currents in the Yangshan area nearly doubled and the current directions were reversed. Surge and significant wave height reached 1.3 m and 8 m, respectively, during the typhoon. Model results agreed well with the observations. Model results revealed that the highest water level occurred at high tide, later than the peak surge, which occurred at low tide. The peak surge occurred at the north coast of the northern island chain, due to the backwater of the chain. The surge in the narrow channel was lower than that in the other areas of the YDH. The current direction in the YDH was slightly southward compared with that during an astronomical tide, due to the winds. A peak surge induced by winds occurred first, followed by wave-induced and the air pressure-induced surges. The wave-induced peak surge occurred at the highest water level. The wind-induced peak surge occurred simultaneously with the peak surge of the storm. Wind has a dominant effect on a storm surge, while wave-current interaction has a minor contribution to the total surge. Wind contributed 87.1% towards the peak surge of the storm, followed by a pressure-induced surge (23.7%) and a wave-induced surge (14.4%), during typhoon Chan-hom.

This paper investigates the diurnal variations of summer precipitation in Shanghai by using the city's hourly precipitation data over a span of 35 years. The result shows that the precipitation peaks twice, i.e., in the morning and in the afternoon. Precipitation in the morning is characterized by light to moderate rain, and that in the afternoon by heavy to super heavy rain. The peak of short-duration precipitation is mostly found in the afternoon and at dusk, and that of long-duration precipitation in the morning. Most of the precipitation events in Shanghai are of a short duration of 2-3 hours. Basically, the precipitation is spatially distributed in three areas: the eastern coastal and central urban area, where the precipitation peaks mostly in the afternoon, the southern coastal area, where the precipitation peaks both in the afternoon and during the night, and the western area, where long-duration precipitation accounts for a much larger proportion than the other two areas.

The finite-volume community ocean model (FVCOM) was used to establish a high-resolution numerical model based on the latest bathymetry data and unstructured mesh. The three-dimensional characteristics of the tidal current and residual current in Yangshan Harbor after the construction of the harbor were studied. Model results indicated that the speed of flood tide was faster than that of the ebb tide in the west of the narrow, and the performance of the east was opposite. The speed in the south of the islands was higher than that in the north. High velocity region and circulation phenomenon appeared at the narrow entrance of the tidal channel, and the peak speed reached 2.88 m/s at the surface level during flood tide. In the north and south areas of the islands, eddies were formed during the flood slack tide, with the northward current at surface and southward current at bottom. And the direction was opposite during ebb slack tide. A circulation existed with the southward current at surface and northward current at bottom during ebb tide at the deep-water channel. The directions of the M2 tidal ellipses were controlled by the coastlines under the influence of the project. The tidal choking effect increased after the construction of the harbor. The residual current was dominated by seaward in Yangshan Harbor sea area, but landward residual current existed in the channel. Separation of residual current appeared at the narrow entrance of the tidal channel. The stagnation point moved eastward.

Over the years, with the advancement in hematology analyzer technology, the use of fluid analysis method has seen a drastic increase in clinical examinations. Cell counting and classification in independent body fluid analysis method are conducted by semiconductor laser flow cytometry and nucleic acid fluorescence staining techniques. This study is to evaluate the efficacy of Sysmex XN-1000 hematology analyzer in cell counting and to screen malignant cells with serous cavity effusion. Specimens (N = 206) with serous cavity effusion from our hospital were included in this study. Manual and instrumental methods for cell counting, nucleated cell classification, and high-fluorescent cells (HFC) were used in this study. The correlation between RBC, nucleated cell count (NUC), the percentages of polymorphonuclear cell (PMN%), and mononuclear cells (MN%) was statistically analyzed using manual and instrumental methods. The regression equations of RBC, NUC, PMN%, and MN% in the manual and instrumental methods were RBC y = 0.88x + 426.4; NUC y = 0.85x + 33.4; PMN% y = 0.91x + 4.2; and MN% y = 0.91x + 5.1. Correlation coefficient R-2 was 0.99, 0.98, 0.90, and 0.90 (P <. 001). ROC curve analysis showed that when the cut-off value of HFC% was 4.4% and HFC# was 24.5/mu L, area under curve (AUC), sensitivity, specificity, and 95% confidence interval were 0.707, 0.792, 0.558, 0.637-0.777; 0.708, 0.753, 0.550, 0.635-0.780, respectively. XN-1000 hematology analyzer body fluid method can accurately and rapidly count cell and nucleated cell classification with serous cavity effusion. HFC can indicate the possible existence of malignant cells; however, further investigations are required to validate its efficacy.

The JAK2 V617F mutation is common in patients with Philadelphia-negative chronic myeloproliferative neoplasms, but few cases of the JAK2 V617F mutation have been described in Philadelphia-positive chronic myeloid leukemia (CML) patients. Here, we report a 21-year-old female who presented with phenotype of CML in whom BCR-ABL transcript and JAK2V617F mutation co-occurred. These findings were determined through cytogenetic analysis, fluorescence in situ hybridization, and allele-specific (AS) PCR. The patient’s BCR-ABL transcript disappeared after 6 months of treatment with imatinib, while the JAK2V617F mutation remained positive. We discuss this case with reference to the current literature.

Objective To develop a simple predictive model for significant fibrosis and cirrhosis in chronic hepatitis B (CHB) using the routine hematological parameters of a complete blood count. Methods A total of 458 eligible CHB patients who had undergone a liver biopsy were randomly divided into two cohorts: an estimation group (n = 310) and a validation group (n = 148). Liver histology was assessed according to the Metavir scoring scheme. All common demographics, hematological parameters, HBeAg status, HBV DNA, and liver biochemistry were analyzed. Results Based on routinely available clinical parameters (age, sex, HBeAg status, HBV DNA, common hematological parameters of a complete blood cell count), a model for predicting significant fibrosis (Metavir score ≥2) in the estimation group was derived using platelets and red cell distribution width (RDW), and another model for predicting cirrhosis (Metavir score = 4) was derived using platelets, RDW and hemoglobin. A novel index, the RDW to platelet ratio (RPR), was developed to amplify the opposing effects of liver fibrosis on the RDW and platelets. The AUCs of the RPR for predicting significant fibrosis and cirrhosis were 0.825 and 0.884, respectively, which is superior to the AAR, FIB-4 and APRI in the estimation group. Compared with the two derived models, the RPR has a comparable predictive power for significant fibrosis and cirrhosis. Using optimized cutoffs (0.10 and 0.16), the RPR accurately predicted 63.1% of cases with significant fibrosis and 73.7% of cases with cirrhosis and accurately excluded 85.5% of the cases with mild fibrosis and 93.0% of the cases with no cirrhosis. Conclusion The RPR, a routinely available, inexpensive and easily calculated index, can predict significant fibrosis and cirrhosis in CHB patients with relatively high accuracy. The application of this index may reduce the need for liver biopsy in CHB patients.

BACKGROUND:Automated hematology analyzers are used to perform cell counts in body fluids. However, little is known about how the results compare between different analyzers. METHODS:A single batch of serous fluid samples was used to evaluate the cell counting performance of 3 hematology analyzers: CD 3700, XE 2100, and LH 750. Two hundred and seventy four serous fluid samples were used to evaluate the accuracy of the analyzers and to compare the results between different analyzers. RESULTS:The precision and linearity of the 3 analyzers were acceptable for both white blood cell counts and red blood cell counts with a low carryover rate. The limits of detection for white blood cells with the CD 3700, XE 2100, and LH 750 analyzers were 0.033×10(9)/l, 0.07×10(9)/l, and 0.20×10(9)/l, respectively. Performing background counts had no influence on cell counts for any of the analyzers. For those samples over the limit of detection, there was agreement between the automated and manual counting methods. There were also reasonably comparable cell count results between the 3 analyzers. CONCLUSIONS:When the serous fluid cell counts are over the limit of detection, the analyzers produce accurate test results. Additionally, the results are comparable between the 3 hematology analyzers.

Weak T-cell reactivity to the hepatitis B virus (HBV) is believed to be the dominant cause of chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). However, it is still unclear how early antiviral therapy affects cellular immune responses during sustained telbivudine treatment. In order to investigate this issue, we measured detailed prospective clinical, virological, and biochemical parameters, and we examined the frequency of T cell subgroups as well as the ability of peripheral blood mononuclear cells (PBMC) to respond to stimuli at five protocol time points for 51 CHB patients who received telbivudine therapy for one year. The preliminary data from this study revealed that effective-treated patients showed an increased frequency of peripheral blood CD4(+)T lymphocytes, an augmented proliferative response of HBV-specific T-cells to the hepatitis B core antigen (HBcAg), and the induction of cytokines, such as interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) release at the site of infection compared to non-responsive patients. Enhanced HBV-specific T-cell reactivity to telbivudine therapy, which peaked at treatment week 12, was confined to a subgroup of effective-treated patients who achieved greater viral suppression.

Being overweight or obese promotes microalbuminuria and increases the risk of chronic kidney disease. This study aimed to develop a mathematical model to estimate the risk of microalbuminuria in overweight Chinese men. Urine albumin/creatinine ratio and metabolic variables were assessed in 1179 subjects, randomly divided into estimation and validation groups that were comparable with respect to all variables. Regression analysis identified body mass index, systolic blood pressure, fasting plasma glucose and blood uric acid as significant variables; these were used to develop a mathematical model for estimating the risk of microalbuminuria. The model generated a receiver-operating characteristic curve indicative of strong predictive accuracy for microalbuminuria (area under the curve, 0.81). A probability cut-off point of 0.50 resulted in global predictive values for microalbuminuria of 86.4% and 84.1% in the validation group (n = 354) and in all subjects, respectively. This model provides a beneficial tool for identifying overweight Chinese men at risk of microalbuminuria; additional studies are required to examine the predictive ability of the model further.

ABSTRACT A multiplex real-time PCR assay was developed to simultaneously detect and discriminate influenza A virus subtypes, including novel H1N1 (2009) and seasonal H3N2 virus, influenza B virus, and respiratory syncytial virus (RSV) in a single test tube, with detection sensitivity and specificity of 99% and 100%, respectively, for the four pathogens.

Background: Obesity promotes progression to microalbuminuria and increases the risk of chronic kidney disease. Current protocols of screening microalbuminuria are not recommended for the overweight or obese.Design and Methods: A cross-sectional study was conducted. The relationship between metabolic risk factors and microalbuminuria was investigated. A regression model based on metabolic risk factors was developed and evaluated for predicting microalbuminuria in the overweight or obese. Results: The prevalence of MA reached up to 17.6% in Chinese overweight men. Obesity, hypertension, hyperglycemia and hyperuricemia were the important risk factors for microalbuminuria in the overweight. The area under ROC curves of the regression model based on the risk factors was 0.82 in predicting microalbuminuria, meanwhile, a decision threshold of 0.2 was found for predicting microalbuminuria with a sensitivity of 67.4% and specificity of 79.0%, and a global predictive value of 75.7%. A decision threshold of 0.1 was chosen for screening microalbuminuria with a sensitivity of 90.0% and specificity of 56.5%, and a global predictive value of 61.7%. Conclusions: The prediction model was an effective tool for screening microalbuminuria by using routine data among overweight populations.

Background: Few studies have examined the relationships between the prevalence of microalbuminuria and the metabolic risk factors in the general population of China. We performed a population based study to investigate the prevalence of microalbuminuria and its relationships with the components of the metabolic syndrome in Hangzhou, China.Methods: The subjects of this cross-sectional study were the individuals from 19 to 87y. The metabolic syndrome was defined based on the criteria of the Chinese Diabetes Society (CDS). Microalbuminuria was defined as a urine albumin-creatinine ratio of 30 to 300 mg/g.Results: A total of 2985 subjects (average age of 44 y) were analyzed. Among them, the prevalence of the metabolic syndrome and microalbuminuria was 12.6% and 8.8%, respectively. Microalbuminuria prevalence rate was significantly higher in the population >60 y than <60 y. The prevalence of MAU in the group with metabolic abnormalities was significantly higher than the control group, and the prevalence rate of MAU in the metabolic syndrome group reached up to 20.3%. There was a significantly positive correlation between the prevalence of microalbuminuria and the corresponding components of the metabolic syndrome (P<0.001).Conclusions: Microalbuminuria was highly prevalent in the middle-aged and elderly Chinese population in the city of Hangzhou. There is an increasing likelihood of having microalbuminuria if subjects have the metabolic syndrome. Early screening strategies for prevention and treatment of MAU are strongly suggested, especially in the population >60 y and the ones with metabolic abnormalities. (C) 2010 Elsevier B.V. All rights reserved.